All eyes will be on Mesereau, best known for winning acquittal for Jackson in 2005 at his six-month trial in California on more than a dozen child molestation charges.
Besides Mesereau, lawyers Kathleen Bliss and Sam Silver will represent Cosby, according to a statement by Andrew Wyatt, Cosby's publicist.
Comedian Bill Cosby has reappeared in court for a hearing in his sex assault case, with fans shouting messages of support as he arrived with his legal team.
Cosby's second trial on three counts of aggravated indecent assault stemming from an encounter with Andrea Constand at his home outside Philadelphia in 2014, is set to begin November 6.
The three will replace Brian McMonagle, a top defense attorney from Philadelphia, and Los Angeles defense lawyer Angela Agrusa, who had been in the case since Cosby's arrest on December 30, 2015.
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Cosby will be retried on felony sexual assault charges following a mistrial in June.
Cosby, 80, was long beloved by US television audiences for his family-friendly style of comedy, before dozens of women came forward to accuse him of a series of sexual assaults dating back to the 1960s.
Cosby has maintained his innocence, saying his relations with Constand were consensual.
Montgomery County Judge Steven O'Neill is expected to release both McMonagle and Agrusa from the case Tuesday. The two led Cosby's legal team at his June trial, which ended in a mistrial after the jury was unable to reach a unanimous verdict.
But the trial irrevocably damaged the once towering icon of United States popular culture, loved by millions as "America's Dad" and best known for his seminal role as a father and obstetrician on hit 1984-92 TV series "The Cosby Show".