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Sweden international Ibrahimovic sat out Wednesday's 2-1 home loss to Sassuolo with a muscular problem and is not ready to return for Monday's Serie A trip to Stadio Olimpico.
The 39-year-old, who this week signed another 12-month extension with Milan, also missed the recent win against Genoa through suspension.
Rafael Leao filled in for Ibrahimovic in those two matches, but Mandzukic - a second-half substitute in both games - is in line for a first league start since joining in January after shaking off an injury issue of his own.
"Ibrahimovic is better but he won't be there tomorrow. He should be back for the following match," Pioli said at a pre-match news conference on Sunday.
Former Juventus striker Mandzukic has featured seven times in total for Milan, his only start coming in the 2-2 Europa League last-32 first leg with Red Star Belgrade in February.
