The song titled "F.U." is to be made available digitally Monday, exclusively through iTunes.
"The music may have mellowed but Denis Leary has not," the label said in a news release. "Leary has some feelings to express with his new single 'F.U.' Recorded live with his band The Enablers, the single also features the Rehab Horns."
Comedy Central Records also released Leary's digital single "At the Rehab," in which he calls out pop-culture icons by name along with their accompanying substance-abuse problems set to an up-tempo calypso beat.
Leary has appeared in more than 30 feature films and stars in the FX television series "Rescue Me," for which he also serves as writer and producer.