ER actor Mekhi Phifer paid tribute, writing: "What a special spirit we have all lost!" Co-star Parminder Nagra said the news was "so sad".
Thompson, who was in ER from 1994 to 2009, had major heart surgery in 2009.
He also appeared in 1997 film Romy and Michele's High School Reunion alongside Lisa Kudrow and Mira Sorvino.
Other roles included parts in the films CB4, a comedy starring Chris Rock, and Fear of a Black Hat, a mockumentary about a hip-hop group, both in 1993.
Actor Scott Baio also paid tribute, as did Neal Baer, a doctor and writer for some of ER's first season.
ER actress Kellie Martin added that she "loved working with him", while actor Terry Wilkerson said: "Even before diversity was popular he made it on one of the biggest shows on network."
Thompson's brother Marshawn told TMZ he was found "unresponsive at home" on Thursday morning, but that no official cause of death had been established.
Another brother, Emmery, posted: "My Big Brother! God is with you. I will miss you."