OBJECTIVES: While the substantial health care cost of depression in the workplace is well documented, less is known about the impact of depression severity on workplace burden. The objective is to document workplace burden of major depressive disorder (MDD) by severity.  METHODS: Using U.S. data from the National Comorbidity Survey-Replication, workforce respondents (n=4465) were classified into clinical severity categories (not clinically depressed, mild, moderate, severe) using standard scales (CIDI/QIDS-SR).  Outcomes included employment status (employed, disabled, unemployed), workplace performance (measured as hours worked, self-rated performance, days of missed work), and workplace burden (estimated by multiplying work hours lost by self-reported hourly income, from HPQ).  Outcomes were compared across depression severity groups using multivariate models that adjusted for demographic characteristics.  Total monthly US burden of reduced work and performance was estimated through extrapolation using government workforce statistics. RESULTS: Among the 539 depressed respondents, 13.8% were mild, 38.5% moderate and 47.7% severely depressed.  Respondents shared similar demographic characteristics across severity levels.  Depressed respondents were 2.6 times more likely to be unemployed/disabled than non-depressed respondents (p<0.001).  The prevalence rates of unemployment/disability increased with depression severity: 15.7%, 23.3% and 31.3% for mild, moderate and severely depressed respondents respectively (p<0.01).  Moderately and severely depressed employed respondents were 4-5% less productive than mildly depressed/non-depressed respondents (p<0.01).  Severity is negatively associated with work performance.  Compared to non-depressed respondents, mildly depressed respondents have reduced monthly workplace performance by 3.0 hours (not statistically significant), vs.12.0 hours (14.8 hours) for moderately (severely) depressed respondents (p<0.001)   The monthly cost of lost performance was $188 ($199) per moderately (severely) depressed worker; the total monthly U.S. burden of reduced work and performance is $2.1 billion/month. CONCLUSIONS: Among MDD respondents in the workforce, there was a positive association between depression severity and rates of unemployment and disability.  Depression is also negatively associated with work performance.