Over 1.5 million Ugandans are HIV-infected, or 7% of its population, of whom 50% are on antiretroviral therapy [1]. Depression is common among people living with HIV in sub-Saharan Africa (SSA), with rates of clinical depression ranging from 10 to 20% [2, 3], and an additional 20–۴۰% having elevated depressive symptoms [2, 4]. Depression has been associated with lower immune function or CD4 count [5], higher HIV viral load [6], greater likelihood of mortality [7, 8], and worse immunologic and virologic response to antiretroviral therapy (ART) [9, 10]. Aside from the mental and physical health consequences of depression, it may also have a role in the economic well-being of people living with HIV, as depression has been associated with lower work productivity and unemployment in this population [11, 12]. Uganda’s latest employment rate was just 48% [13], and the poverty and literacy rates were 20% [14] and 73% [15], respectively. The vast majority of the population resides in rural settings and much of the labor force is in the informal labor market (e.g., small microenterprises and subsistence farming or fishing) and thus has no access to government social security safety net mechanisms. Drawing on social cognitive theory [16], depression may influence work-related outcomes through its effects on work-related self-efficacy or confidence in being able to work and function well in the work environment. Consistent with depression being one of the most disabling medical diseases [17], common symptoms of depression such as lack of motivation, hopelessness, poor concentration, and fatigue may diminish self-efficacy and make it difficult to work and perform productively. Furthermore, it is reasonable to posit that by alleviating depression, depression treatment may improve motivation and self-efficacy to engage in work-related activity. Improved mental health has been associated with improved economic outcomes in low- and middle-income countries [18], but few studies have been conducted with people living with HIV. In a prior study, we found that antidepressant treatment for people living with HIVin Uganda with major depression resulted in reduced work-related impairment and increased work self-efficacy, but not actual engagement in work activities [19], and it did not assess amount of hours worked or income earned. This paper reports findings from a cluster randomized controlled trial of two depression care models for people living with HIV in Uganda, in which depressed HIV clients were followed prospectively for 12 months. Prior analyses from this study revealed that 63% of clinically depressed clients received antidepressant therapy and that 76% of depressed participants achieved full remission of depressive symptoms or depression alleviation by the end of the study [20]. For this paper, we examined whether depression alleviation was associated with work- and economic-related outcomes, specifically amount of hours worked and income earned. We also assessed whether these relationships were mediated by work self-efficacy and if the results differed between those with major and minor depression. Separate analyses for those with major versus minor depression will enable our findings to inform the importance of depression care models addressing less severe forms of depression and not only depression that meets criteria of a clinical disorder.