Nonsteroidal anti-inflammatory drugs (NSAIDs), which are used widely to manage pain, are known to inhibit cyclooxygenase, but details of the mechanisms of NSAID action remain unclear. We investigated the ability of three NSAIDs (indomethacin, loxoprofen, and etodolac) to eliminate and inhibit free radicals. Superoxide scavenging activity of these NSAIDs was measured in vitro by electron spin resonance spectrometry using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as a spin trap. Electron spin resonance demonstrated that formation of superoxide-DMPO spin adduct was completely inhibited by two nonselective cyclooxygenase inhibitors, indomethacin (3 mmol) and loxoprofen (3 mmol). The electron spin resonance study also demonstrated that the formation of superoxide-DMPO spin adduct was strongly inhibited by a selective cyclooxygenase-2 inhibitor, etodolac, in a concentration-dependent manner. These results indicate that NSAIDs, including indomethacin, loxoprofen, and etodolac, have direct superoxide scavenging activity.