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One night of total or partial sleep deprivation (SD) produces a temporary remission in up to 60% of patients with major depression, yet mechanisms remain unclear. We investigated whether the antidepressant effects of SD are caused, even partially, by an improvement in anxiety. As part of a functional magnetic resonance imaging study, 19 unmedicated major depression patients and eight controls completed the Spielberger State/Trait Anxiety Inventory (STAI) (state version) at baseline and sleep-deprived scanning sessions. We found (1) greater anxiety in patients than controls; (2) no baseline or SD STAI difference between responders and nonresponders; (3) no STAI change with SD in any subject group; and (4) no significant correlation between any STAI and Hamilton Depression Rating Scale measures. Our findings did not provide support for an anxiolytic process associated with the antidepressant effects of SD.