Shortly after take-off on 14 August 2005, Nicosia air traffic control (ATC) lost contact with the pilots operating the flight, named Olympia; it eventually crashed near Grammatiko, Greece, killing all 121 passengers and crew on board.

The negligent nature of the accident led to lawsuits being filed against Helios Airways and Boeing, with the former also being shut down by the Government of Cyprus the following year.

The first officer was Pampos Charalambous (Greek: Πάμπος Χαραλάμπους), a 51-year-old Cypriot pilot who had flown exclusively for Helios for the previous five years, accruing 7,549 flight hours throughout his career (3,991 of them on the Boeing 737).

However, Merten, already experiencing the onset of hypoxia's initial symptoms,[3]: 135  disregarded the question, and instead asked in reply, "Where are my equipment cooling circuit breakers?

[7] They intercepted the passenger jet at 11:24 while it was undergoing the sixth loop of the holding pattern and observed that the first officer was slumped motionless at the controls, and the captain's seat was empty.

[3]: 18 At 11:49, flight attendant Andreas Prodromou (Greek: Ανδρέας Προδρόμου) entered the cockpit and sat down in the captain's seat, having remained conscious by using a portable oxygen supply.

[3]: 139 [9] Early media reports erroneously claimed his girlfriend and fellow flight attendant, Haris Charalambous (Greek: Χάρις Χαραλάμπους), was also seen in the cockpit helping Prodromou try to control the aircraft.

[11] However, the official investigation report published in October 2006 said the F-16 crew only saw one male in the cockpit and did not mention DNA evidence.

[3]: 139  However, he succeeded in banking the plane away from Athens and toward a rural area as the engines flamed out, with his actions meaning that there were no ground casualties.

[3]: 51–52 [15][16] The CVR recording enabled investigators to identify Prodromou as the flight attendant who entered the cockpit to try to save the plane.

[3]: 113 The mother of First Officer Charalambous claimed that her son had repeatedly complained to Captain Merten about the aircraft getting cold.

[23] On 29 August 2005, Helios Airways announced successful safety checks on their Boeing fleet and put them back into service.

These images, depicting a Boeing 737 with Helios Airways livery accompanied by F-16s, were found to be fabricated; the aircraft depicted in the image was 5B-DBH, nicknamed Zela,[25] a Boeing 737-800 that was in service with Helios Airways at the time of the accident[26] identified by its overwing exits, longer fuselage, and trailing edge wingtips.

[27] In March 2011, the Federal Aviation Administration in the United States released an Airworthiness Directive requiring all Boeing 737 aircraft from −100 to −500 models to be fitted with two additional cockpit warning lights.

[31] On 23 December 2008, Helios Airways itself and four of its officials were charged in Cyprus with 119 counts of manslaughter, and of causing death by recklessness and negligence.

The panel of judges hearing the case ruled that there was no "causal association between the defendants, and the negligence they were charged with for the fatal accident.

[35][36] In December 2011, shortly after the end of the case in Cyprus, a new trial began in a Greek magistrate's court in which Pantazis, Kikkides, Stoimenov, and Helios Airways chief engineer Alan Irwin were charged with manslaughter.

[35] In April 2012, all were found guilty and sentenced to ten years' imprisonment, and remained free on bail pending an appeal.

[29] Greek investigators blamed the crash of Flight 522 on human error, after the aircraft failed to pressurize after taking off from Larnaca.

Prosecutors in both Greece and Cyprus blamed airline officials for cutting corners on safety operations, while also arguing that they failed to act on advice that the pilots did not meet the necessary aviation standards.

[38] Relatives of the dead filed a class action suit against the Cypriot government—specifically the Department of Civil Aviation (DCA)—for negligence that led to the air disaster.

They claimed that the DCA had ignored airlines' loose enforcement of regulations, and that in general the department cut corners when it came to flight safety.

[31][needs update] The Discovery Channel Canada/National Geographic TV series Mayday featured the accident in a season 4 episode titled "Ghost Plane".

[9] The TV series Ghost Whisperer featured a two-part special called “Free Fall” and “The One”, where a passenger plane is flying around in the air due to everyone on board having died from a lack of oxygen.