Abstract Background Context It has been proposed that depression plays an important role in the course of low back pain; however, there is considerable uncertainty on its predictive value. Purpose This systematic review aims to investigate the effect of depression on the course of acute and subacute low back pain. Study Design This is a systematic review. Methods We searched the following databases using optimized search strategies: AMED, CINAHL, EMBASE, Health & Society Database, LILACS, MEDLINE, PsycINFO, Scopus, and Web of Science. We only included prospective studies that investigated a cohort of participants with acute or subacute non-specific low back pain (pain of less than 12 weeks' duration). The prognostic factor of interest was depression or symptoms of depression assessed at baseline. The outcomes of interest included pain intensity, chronicity (non-recovery from low back pain), disability, return to work, health-related quality of life, and overall patient satisfaction. Two independent reviewers selected the studies, extracted the data, and assessed the methodological quality of the studies that were included. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors declare no conflicts of interest-associated biases. Results Seventeen articles reporting 13 cohort studies were included in this review. There was considerable variability between studies in terms of the method of assessment of depression and low back pain, statistical methods, and follow-up length, which precluded the quantitative synthesis of the results. Definition of outcomes varied across studies, but overall they could be divided into work-related outcome measures, followed by disability, pain, self-perceived recovery, and mixed outcomes. Eleven out of 17 articles (or 8 out of 13 cohorts) reported that symptoms of depression at baseline are related to worse low back pain outcomes (measured in various ways) at follow-up, and the effect sizes (odds ratio OR) ranged from 1.04 to 2.47. Only two studies that did not find a statistically significant association reported quantitative results: OR=1.03, 95% confidence interval (CI) 0.98–1.08; and OR=1.02, 95% CI 0.99–1.06. All included studies, regardless of statistical significance, showed an effect in the direction of harm. Conclusions Although a definitive answer on the effect of depression on the course of low back pain is not available, the findings of this systematic review suggest that depression might have an adverse effect on the prognosis of low back pain. Future large studies that enroll an inception cohort and that employ a standardized method for assessing depression and low back pain are needed.