Chelsea pick youngster Mikel Jon Obi ahead of veteran Claude Makelele for the crucial midfield holding role against Valencia at Stamford Bridge.
England midfielder Joe Cole is on the bench after a lengthy spell on the sidelines with a fractured foot, while Salomon Kalou replaces the injured Arjen Robben on the left flank.
Valencia striker David Villa, a former transfer target for the Blues, leads the attack for the Spaniards.
Teams:
Chelsea: Cech; Diarra, Carvalho, Terry, Cole; Obi Mikel, Ballack, Lampard, Kalou; Drogba, Shevchenko.
Valencia: Canizares; Miguel, Ayala, Moretti, Del Horno; Joaquin, Albelda, Albiol, Vicente; Silva, Villa.
Man Utd hand a surprise start to Ole Gunnar Solskjaer, who is preferred ahead of Alan Smith and the barely-fit Louis Saha to fill the vacancy created by Park Ji-sung's knee injury.
John O'Shea slots in at right-back to allow Wes Brown to partner Rio Ferdinand in central defence.
Roma's side includes three Italian World Cup winners, including Manchester-born midfielder Simone Perrotta.
Teams:
Roma: Doni; Cassetti, Mexes, Chivu, Panucci; De Rossi; Wilhelmsson, Taddei, Perrotta, Mancini; Totti.
Man Utd: Van der Sar; Brown, Ferdinand, O'Shea, Heinze; Ronaldo, Carrick, Scholes, Giggs; Rooney, Solskjaer.