Barcelona said midfielder Xavi Hernandez will miss Tuesday's Copa del Rey match due to a leg injury.
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The team said the Spain international has a muscle pull in his right leg.
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Barcelona host third-division side Cartagena in the return leg of their round-of-32 tie after winning their first meeting 4-1.
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The Spanish champions will also be missing injured forward Lionel Messi and goalkeeper Victor Valdes.
Even without Xavi Hernandez, Barcelona should still go through this fixture. There are still good players