The series follows Louie, a fictionalized version of C.K., a comedian and newly divorced father raising his two daughters in New York City.
According to Nielsen Media Research, the episode was seen by an estimated 1.43 million household viewers and gained a 0.7 ratings share among adults aged 18–49.
As he is tended in the hospital, he calls his ex-wife Janet (Susan Kelechi Watson), informing her that he cannot pick up their children from school, angering her.
In June 2012, FX confirmed that the first episode of the season would be titled "Something Is Wrong", and that it would be written and directed by series creator and lead actor Louis C.K..
Club gave the episode an "A–" grade and wrote, "It's the kind of thing Louie does better than any other show on television, pulling back on a seemingly small moment of attempted connection to reveal a much bigger cosmic picture.
"[5] Alan Sepinwall of HitFix wrote, "'Something Is Wrong' was definitely the most lightweight of the five episodes I got to see in advance – and by that I mean comedy as well as the character and thematic work.
"[6] Roger Cormier of Vulture wrote, "So 'Something is Wrong', the third season premiere of the series that aired last night, was an average episode of Louie, so basically it was only funny, too honest and successfully weird.
"[7] Paste gave the episode a 8.2 out of 10 and wrote, "The show didn't return to the air with guns blazing, letting loose with a torrent of hilarious moments, neither did it really try something new.
As much as there can be one, this was a complete return to form for Louie, a first episode that seems concerned with delivering the same rewards as the past two seasons.
"[8] Matt Richenthal of TV Fanatic gave the episode a 4.6 star out of 5 rating and wrote, "Louie isn't a bad guy by any means, but he's a somber soul and it's his quest to figure out how to be happy - by sticking in a less-than-ideal relationship?