The winger had only played once in La Liga this season due to several injuries. He managed 64 minutes in the 3-2 win against Inter in the Champions League on Tuesday night.
Hazard was expected to occupy the wide left position in Zinedine Zidane's set-up, with Marcos Asensio on the opposite flank. However in the last few hours he's been announced as having tested posted for Covid.
Vinicius may start in place of the Belgian.
Midfielder Casemiro also tested positive, and will also miss out. Casemiro could be replaced by Luka Modric.
Madrid have won their last two consecutive league games, including a win against Barcelona in El Clasico.
Karim Benzema will play from the start, whilst Tuesday's match-winner Rodrygo could enter the game in its latter stages.
Toni Kroos and Federico Valverde are believed to be ready to start in Zidane's central midfield two. Luka Modric was expected to remain on the bench, but could enter the fray now that Casemiro is out.
The back four from Tuesday night's win should remain unchanged. With Ferland Mendy on the left, Sergio Ramos and Rafael Varane central, and Lucas Vazquez filling in at right-back.
Zidane is unable to call upon Nacho, Alvaro Odriozola or Dani Carvajal through injury. Meanwhile, Eder Militao is not available due to testing positive for Covid.