Depression-related costs include a relatively large share of indirect costs. We describe the impact of antidepressant treatment on absenteeism among workers diagnosed and treated for depression. Monthly absenteeism counts from employers were summed in the 6 months before and after the initiation of antidepressant therapy in 630 workers treated for depression with a tricyclic antidepressant or a selective serotonin reuptake inhibitor (fluoxetine, sertraline, paroxetine). Monthly mean absenteeism was compared using pairwise t tests. Absenteeism increased before antidepressant initiation and decreased after the treatment began for all antidepressant cohorts. Absenteeism in the selective serotonin reuptake inhibitor cohorts decreased at similar rates for 4 months but was higher in the paroxetine cohort in months five and six after the treatment initiation. Our data suggest that alternative treatments for depression may have differential impact on indirect costs, but further research is warranted.