Introduction: The present study aimed to review the association between obstructive sleep apnea (OSA) and depression and compare the prevalence of depression among people with and without OSA. Methods: Systematic review and meta-analysis following PRISMA guidelines. We searched for papers published between 1 January 2010 and 20 October 2019 listed on the following databases: Embase, Ovid MEDLINER(R) and PsychINFO. The search terms included a combination of keywords related to sleep apnea and depression. We also completed a manual search of the references listed in the articles retrieved and grouped them according to study design: cross-sectional, case-control and longitudinal. Scale scores were standardised for comparison. Results: Our search strategy yielded 1158 papers, of which 34 were considered suitable of review and 11 reported data that could be used for meta-analysis. Data from the 6 cross-sectional studies found no compelling evidence of an association between OSA and depression (odds ratio = 1.12, 95 % confidence interval, 95 %CI = 0.78, 1.47), but the meta-analysis of 5 longitudinal studies indicated that people with OSA were at greater risk of developing depression during follow-up than those without OSA (non-specific risk ratio (RR) = 2.18, 95 %CI = 1.47, 2.88), although there was evidence of high study heterogeneity (I2 = 72.8 %). Discussion: The results of this systematic review and meta-analysis of observational studies is consistent with the hypothesis that OSA may increase the risk of depression. Sample characteristics and various methodological issues create uncertainty about the validity and generalizability of these associations.