Skeletal muscle satellite cells play an important role in muscle regeneration. Previous work has suggested that nonsteroidal anti-inflammatory drugs may inhibit their activity. We cultured skeletal muscle satellite cells from 9-month-old Sprague-Dawley rats and exposed them to naproxen sodium (a nonselective cyclooxygenase inhibitor), NS-398 (a selective cyclooxygenase-2 inhibitor), and SC-560 (a selective cyclooxygenase-1 inhibitor) for 96 h. Cyclooxygenase-2 inhibition alone resulted in decreased satellite cell proliferation, and inhibition of both cyclooxygenase-1 and cyclooxygenase-2 resulted in decreased satellite cell differentiation and fusion. This study suggests that the cyclooxygenase enzymes appear to play an important part in satellite cell proliferation, differentiation, and fusion and that nonsteroidal anti-inflammatory medication may have an adverse effect on muscle regeneration following injury. The use of a selective cyclooxygenase-2 inhibitor over nonspecific cyclooxygenase inhibitors in the treatment of muscle injuries is not supported.