It would be the first time the two forwards have started a match together on the bench, but the decision would be driven by fitness and workload rather than discipline.
Vinicius has returned from international duty with Brazil after playing in all three of their friendlies in Australia and India. The long-distance travel and heavy workload have left Mourinho assessing whether the winger is ready to start.
The Brazilian has also struggled to find his best form for Real Madrid this season, meaning a spell on the bench could give him a chance to recover physically and mentally before an important period of the campaign.
Mbappe's situation is more straightforward. The France forward has been recovering from a hyperextension of the posterior capsule of his left knee and has started individual training at Real Madrid City.
Even if Mbappe is declared fit for the Villarreal match, Mourinho must decide whether he is ready to handle the intensity of a full game.
Real Madrid have enough attacking options to cope if both stars are rested. Brahim Diaz, Arda Guler and Jude Bellingham can all take on greater responsibility, while Carlos Espi and Yan Diomande are also options depending on Mourinho's tactical plans.
The decision could also be influenced by what lies ahead.
After Villarreal, Real Madrid face Roma, Sevilla and RB Leipzig before the crucial El Clasico against Barcelona on October 25.
Mourinho therefore has to look beyond Saturday's match. Protecting Vinicius and Mbappe now could give Real Madrid a better chance of having both forwards at full strength when the biggest games arrive.
The final decision is expected to depend on how the pair respond in training, but Mourinho is clearly weighing the bigger picture as Real Madrid enter a demanding part of the season.
