McCarthy will be partnered by big George Naoupu, while an athletic back row combination of David Gannon, John Muldoon and Ray Ofisa will continue the hard graft of the loose forwards.
Brett Wilkinson, Ethienne Reynecke and Ronan Loughney will link up in an unchanged front row, with Frank Murphy and Niall O'Connor resuming their half-back partnership. Reynecke and O'Connor are starting a Heineken Cup match for the first time.
Eric Elwood has shown faith by naming an unchanged back-line with David McSharry and Heineken Cup debutant Kyle Tonetti in the centre and Mark McCrea, another newcomer at this level, Tiernan O'Halloran and captain Gavin Duffy making up the back-three.
There is plenty of talent waiting on the bench with Adrian Flavin, Denis Buckley and Rodney Ah You providing front row cover and Michael Kearney and Eoin McKeon covering the loose forwards.
Paul O'Donohoe and Heineken Cup newcomers Matthew Jarvis and Fetu'u Vainikolo add the extra options in the backs.
CONNACHT (v Gloucester): Gavin Duffy (capt); Mark McCrea, Kyle Tonetti, David McSharry, Tiernan O'Halloran; Niall O'Connor, Frank Murphy; Brett Wilkinson, Ethienne Reynecke, Ronan Loughney, Mike McCarthy, George Naoupu, David Gannon, John Muldoon, Ray Ofisa.
Replacements: Adrian Flavin, Denis Buckley, Rodney Ah You, Michael Kearney, Eoin McKeon, Paul O'Donohoe, Matthew Jarvis, Fetu'u Vainikolo.