[7] Wessely's main research interests lie in the "grey areas" between medicine and psychiatry, clinical epidemiology and military health.

[1] Other interests include epidemiology, , medicine and law, history of psychiatry, chronic pain, somatisation,  chemical and biological terrorism and deliberate self-harm.

[9] In the first years after the introduction of the diagnosis chronic fatigue syndrome the condition was often mocked in the media, for example being described as "yuppie flu".

[10] Wessely and his co-workers verified that this stereotype was inaccurate, substantiating an association between autonomic dysfunction and chronic fatigue syndrome[11] and providing reliable data on the prevalence of CFS in the community, showing that it has become an important public health issue.

[15] Wessely and his colleagues, using randomised controlled trials and follow-up studies,[16] developed a rehabilitation strategy for patients that involved cognitive behavioural and graded exercise therapy, that is claimed to be effective in reducing symptoms of CFS (a condition that otherwise lacks a cure or unequivocally successful treatment) in ambulant (non-severely affected) patients.

These beliefs and behaviours interact with the patient's emotional and physiological state and interpersonal situation to form self-perpetuating vicious circles of fatigue and disability...

He used the analogy of a hit-and-run accident in which finding out the manufacturer or number plate of the car that hits you doesn't assist the doctor in trying to mend the injury.

Wessely collaborated with experts in retrovirology at Imperial College London, sharing with them stored DNA samples from the King’s CFS unit, and providing the first proof that XMRV was not the cause of CFS/ME.

[33] He has also suggested that campaigners are motivated "not so much by a dispassionate thirst for knowledge but more by an overwhelming desire to get rid of the psychiatrists"[citation needed] from the area of chronic fatigue syndrome, despite having himself published research which concluded that "the stereotype of CFS sufferers as perfectionists with negative attitudes toward psychiatry was not supported".

[34][35] When asked about severely affected bed-ridden patients, Wessely said "in that kind of disability, psychological factors are important and I don't care how unpopular that statement makes me.

I have speed dial phones and panic buttons at police request and receive a regular briefing on my safety and specific threats."

Wessely gave up research into CFS around 2001, and as of 2011 his clinical work was with members of the armed forces; he said: "I now go to Iraq and Afghanistan, where I feel a lot safer".

which might have at least in part being triggered by stress, specifically troops' anxiety about chemical weapons and vaccines, as well as misinformation about Gulf War syndrome.

Early results showed that there had been no “Iraq War Syndrome”,[47] despite the fact that the Forces had received similar drugs and vaccinations to protect against chemical and biological warfare.

Improvements in record keeping now showed that both anthrax and multiple vaccinations were not associated with medium or long term ill health.

In two recent citation analyses Wessely was rated the most published author on military health, with his colleagues Professors Fear and Greenberg in third and fourth place globally.

[55] As president he has been a regular media spokesperson such as on BBC current affairs programme Panorama,[56] and that killings by those with mental illness are both unusual and declining.

[57] He has argued against making benefits conditional on co operating with mental health treatments,[58] as subsequently accepted by the Carol Black report and warned psychiatrists against diagnosing Donald Trump, no matter how tempting this may be.

He was a co-author of an influential Cochrane Review showing that the conventional intervention for disaster survivors – to offer immediate psychological debriefing – was not only ineffective, but possibly did more harm than good.

He argued that the skies would be safer if pilots felt that the best way to be able to continue their careers was by being open and honest about their mental health, and not covering up, which would be the consequence of a lifetime ban.

[84] In January 2023 he was appointed as a Non Executive Director on the Board of NHS-England  NHS England [85] In 2015 he led the bid between King’s College London, Newcastle University and University of East Anglia for a new Health Protection Research Unit (HPRU) in Emergency Preparedness and Response in 201R, becoming its first director and leading it to renewal in 2020, before handing over the Directorship to Professor James Rubin in 2022 .

The unit continued a major theme of Wessely’s research into how populations and people react to disaster and adversity, adding the Salisbury Novocok incident Public responses to the Salisbury Novichok incident: a cross-sectional survey of anxiety, anger, uncertainty, perceived risk and avoidance behaviour in the local community [87] risk communication, organisational responses to stress, and latterly a large portfolio of research into Covid-19, including psychological impacts of quarantine Coronavirus: The psychological effects of quarantining a city  – The BMJ, a Feb 2020 systematic review of the likely impact and how to reduce it, which has been cited over 10,000 times since publication [88] The psychological impact of quarantine and how to reduce it: rapid review of the evidence – The Lancet, work on Pmoral injury and the health of the NHS workforce during the pandemic[87] Managing mental health challenges faced by healthcare workers during covid-19 pandemic[89] The BMJ, conspiracy theories and Covid, and other aspects of health protection.

He has been a guest on Private Passions,[92]  The Life Scientific,[93] and  on the BBC celebrity radio show Desert Island Discs in March 2021.

[99] Wessely has co-authored books on CFS, psychological reactions to terrorism, randomised controlled trials, and a history of military psychiatry, From Shell Shock to PTSD.

[104] The award is given to individuals who have promoted sound science and evidence on a matter of public interest, with an emphasis on those who have faced extreme difficulty or opposition in doing so, as Wessely has done in researching neuropsychiatric elements to CFS despite alleged threats to his life.

[105] To balance these criticisms academic supporters would point out that he was appointed[106] as a Foundation Senior Investigator of the National Institute for Health and Care Research (NIHR), which is given on very strict criteria[107] including analysis of metrics/citations.