The 26-year-old suffered discomfort in his right knee during Barcelona's 4-1 victory over Real Betis on Sunday, but still managed to score twice in the second half.
After receiving the results of tests from Barcelona's medical team, the Spanish Football Federation have opted to take Fabregas out of their squad.
Uncapped defender Marc Bartra, a team-mate of Fabregas at club level, has been called up as a replacement.
Reigning world and European champions Spain face Equatorial Guinea on November 16 and South Africa three days later.
Fabregas boasts 86 caps for his country, having made his debut as a teenager in 2006.
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