Previous studies indicate that selective serotonin reuptake inhibitors (SSRIs), including fluoxetine, fluvoxamine, citalopram and paroxetine, suppress rapid eye movement sleep, and increased nocturnal arousals. There has been no published report of the impact of sertraline on the sleep of depressed patients. This study examines such effects. Forty-seven patients with major depressive disorder, randomized to double-blind treatment with sertraline or placebo, completed sleep studies before and after 12 weeks of pharmacotherapy. Groups were compared using multivariate analyses of covariance and/or analyses of covariance to examine 4 empirically defined sets of sleep measures. Compared to the placebo-treated group, patients who received sertraline experienced an increase in delta wave sleep in the first sleep cycle and prolonged rapid eye movement (REM) sleep latency. Although, sertraline therapy decreased the average number of REM periods (from 3.86 to 2.40), the activity of both REM period 1 and REM period 2 was significantly increased. Aside from an increase in sleep latency, sertraline therapy was not associated with a worsening of measures of sleep continuity. There was also no significant difference between the groups on a measure of subjective sleepiness. These findings are both similar and different from those observed in previous studies of other SSRIs. The increase in delta sleep ratio and consolidation of REM sleep may have some other clinical implications. However, the generalizability of these findings is limited because of a number of reasons. Further studies are needed to examine the effects of SSRIs in acute treatment of depressed patients with severe insomnia, and the relationship of acute changes and relapse prevention of recurrent depression.