OBJECTIVE: To assess indirect costs of work loss associated with bipolar disorder and major (unipolar) depression. METHOD: From MEDSTAT's employer-based MarketScan(c) database for year 2000, workers (mean age 42 ± 9) with a primary ICD9-CM diagnosis of bipolar disorder (N = 740), major depression (N = 6314), and one-to-one matched controls with no psychiatric diagnosis were identified. Work loss parameters were absence hours and payments for short-term disability and worker compensation. RESULTS: Mean annual absence hours were 55 (± 49) for the bipolar group vs 21 (± 27) for controls (P = 0.009), and 53 ( ± 154) for the unipolar depression group vs 24 (± 48) for controls (P <0.0001). Mean short-term disability payments were $1231 (± 3424) for the bipolar group vs $131 ( ± 967) for controls (P <0.0001), and $741 ( ± 2873) for the unipolar depression group vs $178 ( ± 1309) for controls (P <0.0001). Mean worker compensation payments were $554 ( ± 4231) for the bipolar group vs $228 ( ± 2289) for controls (P = 0.15), and $518 (± 4814) for the unipolar depression group vs $220 ( ± 2449) for controls (P = 0.0001). CONCLUSIONS: Bipolar disorder and major (unipolar) depression significantly increased work loss. Patients with bipolar disorder may exhaust their sick leave and go onto short-term disability more frequently than those with unipolar depression.