The westerners' squad includes a number of players who have recently come through the Connacht Academy, including Conor Higgins, Dermot Murphy and Tiernan O'Halloran, who is poised to make his debut on the right wing.
Strong-running centre Niva Ta'auso, who missed last week's game against the Dragons with a hand injury, looks set to return to the starting line-up.
This is Connacht's 14th season in Europe's second tier competition and Madrid are the second Spanish side they have faced.
They had Centransa El Salvador in their pool two years ago, claiming a 75-6 win at the Sportsground and a 60-0 success in Spain.
CONNACHT Squad (v Olympus Rugby Madrid) - Backs (10): Fionn Carr, Gavin Duffy, Ian Keatley, Frank Murphy, Tiernan O'Halloran, Conor O'Loughlin, Troy Nathan, Miah Nikora, Niva Ta'auso, Aidan Wynne.
Forwards (13): Andrew Browne, Sean Cronin, Adrian Flavin, Jamie Hagan, Conor Higgins, Ronan Loughney, Mike McCarthy, John Muldoon (capt), Dermot Murphy, Johnny O'Connor, Michael Swift, Bernie Upton, Brett Wilkinson.