The Argentina striker suffered a bruised leg in training on Thursday and is not expected to play any part at Stadio Friuli.
Higuain scored a hat-trick in a 4-2 win over Lazio last weekend, but the Naples outfit revealed on their official website that he is not likely to be fully fit for "a few days".
The expected absence of the former Real Madrid man could open the door for Duvan Zapata to start against Francesco Guidolin's side.
Napoli coach Rafael Benitez will also be unable to call upon Dries Mertens due to suspension, while Juan Camilo Zuniga, Rafael and Christian Maggio are also unavailable.
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