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We present a case of subtotal cavernous sinus thrombosis secondary to Panton-Valentine leukocidin–associated Staphylococcus aureus pyomyositis of the muscles of mastication in a previously healthy child, who was successfully managed with no residual disease. He was found to have a factor V Leiden heterozygous mutation. We highlight the propensity of Panton-Valentine leukocidin Staphylococcus aureus to induce venous thrombosis at any site but with potential for more severe consequences in the head. We highlight pyomyositis as a differential for periorbital cellulitis and discuss the significance of the factor V Leiden mutation.