The captain sat out of Wednesday's 7-1 victory over Bayer Leverkusen in the Champions League and will now undergo a late fitness test.
Barcelona are already without the suspended Gerard Pique and will also have to do without the services of Eric Abidal through injury, which means Sergio Busquets would have to play centre-half if Puyol is ruled out.
In addition, Pep Guardiola will be unable to call upon David Villa, Thiago, Alexis Sanchez, Ibrahim Afellay and Andreu Fontas for the trip to El Sardinero.
With Real Madrid facing Betis on Saturday, Barcelona could head into this weekend's fixture 13 points behind their bitter rivals, who lead La Liga.
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