Argentine winger Perotti, 30, injured his left calf in training on Tuesday and will be out for at least three weeks, according to Italian press reports, while Dutch full-back Karsdorp, 23, will be sidelined for ten days with a thigh injury.
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Perotti, Karsdorp injury blow for Roma
AS Roma will be without injured pair Diego Perotti and Rick Karsdorp for Saturday's game at home to SPAL as well as next week's visit by CSKA Moscow in the Champions League.
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Eusebio Di Francesco's side are sixth in Serie A after winning three consecutive games before the international break.
They will still be without the two players when they face Carlo Ancelotti's second-placed Napoli on October 28.
Roma are second in Champions League Group G, one point behind leaders CSKA after two games, in a section which also includes reigning champions Real Madrid and Viktoria Plzen.
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