Back into the Red Hand side come Peter Harte and Tiernan McCann at the expense of Barry Tierney and PJ Lavery.
Harte makes his return from an injury sustained against Cavan in the Dr McKenna Cup final in late January.
Tyrone will be looking to bounce back from a very poor display against Monaghan in the opening round of the league when they lost out by seven points.
Tyrone’s record against Mayo in the National League in recent years has been very good but with the Mayo men seeing to Kerry last weekend, new manager Noel Connolly they will have to improve greatly on their last weekend’s effort.
Tyrone team: Niall Morgan, Aidan McCrory, Ronan McNamee, Cathal McCarron, Ronan McNabb, Mattie Donnelly, Peter Harte, Colm Cavanagh, Padraig McNulty, Tiernan McCann, Ronan O’Neill, Peter Hughes, Darren McCurry, Sean Cavanagh, Niall McKenna.
Subs: Michael O’Neill, Rory Brennan, PJ Lavery, Connor McAliskey, Danny McBride, Conall McCann, Shay McGuigan, Emmett McKenna, Justin McMahon, Cathal McShane.
Sunday’s game in Castlebar gets underway at 2pm.