Lewandowski suffered a back injury in Sunday's 1-0 defeat at Real Sociedad during which he had a goal controversially disallowed.
Lewandowski's early disallowed strike led to furious debate over whether the Polish forward had been offside or not.
Barcelona coach Hansi Flick said he thought playmaker Dani Olmo would be ready despite feeling unwell overnight, while defender Pau Cubarsi can play despite suffering a cut on his face during the team's Champions League win over Red Star Belgrade on Wednesday.
It was another commanding victory for LaLiga leaders Barcelona who are in an imperious vein of form, scoring 24 goals in six successive wins in all competitions, including thrashings of Bayern Munich and Real Madrid.
Dani Olmo struck twice for Barcelona on his first start after an injury absence as they beat local rivals Espanyol 3-1 on Sunday to move nine points clear at the top of La Liga.
"Honestly I don't see it as extraordinary, even if some people do... when I was little I also looked on from the outside, watching from my house seeing Messi lift Ballons d'Or and thinking it was incredible. Once you are on the inside, you take it normally, naturally, although if I stop to think about it, it's something really big."
The Catalan giants triumphed at the Santiago Bernabeu to snap Madrid's run of 42 matches unbeaten and continue their own revival under the German coach who arrived this summer.
Defending champions Real Madrid are set to host archrivals Barcelona in a LaLiga game at the Santiago Bernabeu tonight.
Kylian Mbappe's start at Real Madrid has been satisfactory, his performances neither spectacular nor underwhelming, but Saturday's La Liga Clasico offers the French superstar a springboard to kick on from.
Barcelona coach Hansi Flick backed reserve goalkeeper Inaki Pena to replace stricken team-mate Marc-Andre ter Stegen on Tuesday, but also said the club must discuss if they will sign a replacement.
Hansi Flick's side extended their winning streak in the league to six games as they bounced back from their 2-1 loss against Monaco in the Champions League on Thursday.
Vinicius Junior's decisive impact helped Real Madrid come from behind to beat a determined Espanyol side 4-1 on Saturday and move a point behind La Liga leaders Barcelona.
Hansi Flick's side have started the season with a perfect record after five La Liga matches but struggled to find their best level against the Ligue 1 side.
Approaching a decade since Barcelona last won the Champions League, the Catalan giants face Monaco in this season's European opener on Thursday aiming to make a statement.
Yamal, who grabbed the spotlight as he helped Spain win their fourth European Championship title in July, scored twice in the first half before Dani Olmo and Pedri secured the win with Flick's side maintaining their unbeaten start to the league season.
Teenage star Lamine Yamal struck twice as La Liga leaders Barcelona thrashed Girona 4-1 on Sunday.
Yamal made his Barcelona debut aged 15 in April 2023 and burst into the limelight last season, becoming a key player for the Catalan giants.
Goalkeeper Marc-Andre ter Stegen said Thursday the end of a 12-year wait to succeed Manuel Neuer as Germany's number one goalie felt like "a balm for the soul".
After scoring the first hat-trick of his career and delivering two assists to guide Barca to a 7-0 demolition of Real Valladolid, Raphinha said that the result showed that the club has the players it needs to be contenders.