Mood and quality of life (QOL) outcomes vary widely in neuropathic pain trials. This may be a result of variable analgesia and other treatment effects. We evaluated the relationship between pain reduction and mood/QOL in neuropathic pain. Pain, side effects, QOL, and mood from a trial of morphine, gabapentin, and a morphine-gabapentin combination were examined. Baseline QOL was impaired according to Short Form Health Survey (SF-36) scores. Baseline mood, according to Profile of Mood States scores, was comparable to that of a nondepressed population. Pain reduction with all three active trial treatments correlated with improved QOL. Pain reduction with morphine and with gabapentin correlated with improved mood. Pain reduction with a morphine-gabapentin combination correlated with improvement in only one of several domains of the Profile of Mood States. Severity of sedation, constipation, and dry mouth during any treatment did not correlate with mood/QOL changes. These results can be interpreted to imply that larger analgesic treatment effect sizes lead to more substantial improvements in QOL and/or mood. However, other beneficial or adverse treatment-related side effects may also affect mood/QOL. Therefore, future studies are needed to also evaluate the impact of treatment-related side effects on mood/QOL in analgesic trials.