The manner of the loss at La Liga's smallest club has undone a lot of the momentum which was built with four consecutive wins prior to the weekend game, and it means Santiago Solari's side will be desperate for a big performance at the Stadio Olimpico.
A win for the European champions would see them through the knockout stages as group winners and bet365 price them at 21/10 (2.05). A draw would see Roma through to the last 16 and a stalemate in the Italian capital is priced at 11/4 (3.75) with the hosts offered at 11/5 (3.20).
Casemiro remains out for Real Madrid, with Dani Ceballos coming into the team in his place on Saturday. Right-back Dani Carvajal came on as a substitute at Eibar after nearly two months out and could return to the starting eleven on Tuesday. Defender Nacho Fernandez remains unavailable through injury.
Roma are without midfielder Daniele De Rossi and winger Diego Perrotti. Centre-back Kostas Manolas is also a doubt after picking up a knock on international duty, although Edin Dzeko should return to the starting eleven after starting Saturday's game on the bench.
Real Madrid produced their best performance of what has been a disappointing season back on Matchday One, sweeping aside Roma 3-0 at the Bernabeu.
Since then Roma have responded with three wins in Group G and put together a solid run domestically, while Madrid have won just six of their subsequent 13 games in all competitions.
Away from home Los Blancos have generally lacked defensive solidity with their last 15 matches on the road seeing them keep just two clean sheets, although they were against modest opposition in Viktoria Plzen and third tier Melilla in the Copa del Rey.
Roma in contrast have won each of their last seven home Champions League matches, although they will have to improve considerably on their weekend showing to win on Tuesday.
Tips and predictions
Both teams to score and over 2.5 goals is offered at 8/11 (1.73) and both sides have been shipping goals of late. Roma to score over 1.5 goals is offered at a tempting 11/10 (2.10) with both teams to score in the first half priced at 5/2 (3.50).
Prices correct at the time of writing. Please gamble responsibly.