Mourinho's charges beat another of his old sides - Inter Milan in their UCL opener - but they trail defending champions Barcelona by six points in LaLiga.
Hosts Roma have won just of their last four games across all competitions ahead of welcoming Mourinho back to the Italian capital.
Roma v Real Madrid team news
Los Blancos edged out a 1-0 home win over Villarreal at the weekend, as Yan Diomande netted his first club goal, with Vinicius Junior sent off.
His subsequent ban does not apply to Europe, so the Brazilian will start in Rome, but Mourinho is expected to recall Denzel Dumfries and Marc Cucurella at full-back.
Real Madrid v Roma predicted lineup
Real Madrid XI: Courtois; Dumfries, Konate, Rudiger, Cucurella; Valverde, Bellingham, Tchouameni; Diomande, Mbappe, Vinicius Junior.
Real Madrid v Roma kick off time
Kick off at the Stadio Olimpico is set at 9pm local time and 8pm in the UK.
Key stat
Real Madrid have won their last four UCL meetings with Roma, in 2016 and 2018, with a score tally of 9-0.