The broadcast will begin with a (RED) Shopathon, where fans can bid on products and "experiences" offered by many of the stars participating in the TV special.
During last year's event, Bono sat down for an interview with Kimmel and told the TV host that his charity organisation had provided medication to 21 million people, but added, "There are still 400 babies born today who need not be born with the virus that was given to their mother in utero."
The rocker predicted that the situation could be fixed by 2020.
"We really believe we can do it," he told Kimmel.
News of Bono's involvement in this year's (RED) benefit comes days after the rock star sparked concern among U2 fans by revealing the band was "going away now" following the end of their "Experience + Innocence Tour".
He made the comment as the group took to the stage at the Mercedes-Benz Arena in Berlin, Germany for the last night of their trek on Tuesday, November 13.
"We've been on the road for quite some time, just going on 40 years, and these last four years have been really something very special for us. We're going away now..." Bono told the crowd.
If he speaks to Kimmel again on Monday night, he is expected to explain his remark.