My Name is Earl starred Jason Lee as the hapless hero
Hit comedy series My Name is Earl and supernatural thriller Medium are among TV shows being axed in a summer cull in the US.
Medium, which starred Patricia Arquette, ran for five seasons and was nominated for several Golden Globes.
Earl's creator Greg Garcia reportedly referred to the news as "being thrown off the Titanic" - a reference to broadcaster NBC's recent poor ratings.
Military-action drama The Unit has also been cancelled by the CBS network.
Ethan Suplee, who played loveable buffoon Randy Hickey in My Name Is Earl, used Twitter to vent his frustration.
"Just got the call that My Name Is Earl has been cancelled," he wrote. "They sure did take their time with that decision... or rather informing us of it."
CBS Studios, which makes Medium for the NBC network, said it was not ready to give up on its show.
In a statement, it blasted the network's decision as "inexplicable to us".
"Medium outperforms many of NBC's renewed shows," it continued.
It is possible that Medium will move to another channel, while My Name Is Earl's producers said their show could be picked up by the Fox or ABC networks.
Shows which have been re-commissioned include spy comedy Chuck and crime procedural Law & Order.