Spain star Fabregas came off during the Blues' League Cup semi-final victory over Liverpool with a hamstring injury and missed the draw with Manchester City and Saturday's win at Aston Villa.
But Mourinho confirmed Fabregas will be back in midfield for the showdown at Stamford Bridge as the Blues aim to maintain their seven-point lead over City at the top of the table.
"I think he [Fabregas] plays Wednesday because on Saturday it was a decision to protect him," said Mourinho. "We didn't want to risk two players at the same time. We risked with Willian and to start two players with a risk is a big gamble and we gambled with only one."
In the absence of Fabregas, Ramires had been selected in midfield, alongside Nemanja Matic, following his own return to full fitness and Mourinho admitted it was a great help to have such quality back-up.
"The best Ramires is back and the best Ramires played against Liverpool, Man City and Aston Villa," Mourinho added. "He is a different profile of player [compared with Fabregas] but he is a fantastic player for us."
Toure has faith Man City can win title
Manchester City midfielder Yaya Toure believes the Citizens can win all of their remaining Premier League fixtures and successfully defend their title.
Manuel Pellegrini's team are seven points behind leaders Chelsea with 14 matches left to play, the first of which is against Stoke City at the Britannia Stadium.
City have failed to win in their last five matches, a run that has coincided with Toure's absence due to Africa Cup of Nations commitments with Ivory Coast.
Toure helped his country win the continental competition on Sunday with a penalty shootout victory over Ghana in the final and is due back in Britain this week.
However, Pellegrini has said it would be "impossible" for Toure or compatriot Wilfried Bony to feature against Stoke and that their return to the Premier League is likely to come against Newcastle United on February 21.
"With my confidence I know football is not about one game or two games, especially in the Premier League," he said. "We have 38 games and if we want to win the title, we have to win all the games.”
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