The Chelsea and Manchester United veterans are the highest-profile names to miss the cut as the Premier League's top teams finalize their group stage rosters.
Essien had been reunited with Jose Mourinho at Chelsea after spending last season on loan at Real Madrid but has been an unused substitute in three of the Blues' first four matches this season and now has missed out on the opening phase of continental play.
Fletcher, meanwhile, has made only 13 appearances for Manchester United since his 2011 diagnosis of ulcerative colitis and looks set to spend more time away from the pitch. The 29-year-old was hoped to be nearing a return to action but his lack of inclusion in David Moyes' group stage squad indicates the Scot may not be ready until 2014.
In August, Fletcher stated he had been practicing a self-imposed exile from the Red Devils' training ground in Carrington as he waited for his surgeon to clear him to return to training.
Youngster Adnan Januzaj, who drew attention during United's tour of Asia this summer, was also left out of the Champions League squad, while new faces Marouane Fellaini and Wilfried Zaha have made the cut.