Dylan Rogers, Adrian Flavin and Brett Wilkinson renew their partnership in the front row with Michael Swift and Mike McCarthy linking up again in the engine room.
Former captain John Muldoon is positioned at blindside flanker with Ofisa wearing the number 7 jersey and big George Naoupu anchoring the scrum at number 8.
In the backs, O'Donohoe replaces the injured Frank Murphy who underwent surgery on his groin earlier this week and is set to miss the next three weeks.
O'Connor will orchestrate the back-line with the youthful talents of David McSharry and Kyle Tonetti in the centre backed up by Tiernan O'Halloran, Fetu'u Vainikolo and skipper Gavin Duffy at full-back.
CONNACHT (v Toulouse): Gavin Duffy (capt); Fetu'u Vainikolo, Kyle Tonetti, David McSharry, Tiernan O'Halloran; Niall O'Connor, Paul O'Donohoe; Brett Wilkinson, Adrian Flavin, Dylan Rogers, Michael Swift, Mike McCarthy, John Muldoon, Ray Ofisa, George Naoupu.
Replacements: Ethienne Reynecke, Denis Buckley, Stewart Maguire, Michael Kearney, Eoin McKeon, David Moore, Miah Nikora, Henry Fa'afili.