•Decreased levels of kynurenine was found in unipolar depression vs. healthy controls.•No significant differences were found in tryptophan levels or kynurenine/tryptophan ratios in patients with unipolar or bipolar disorder vs. healthy controls. Activation of the kynurenine pathway is one of the described mechanisms by which inflammation can induce depression. It involves multiple pathways including interference with the bioavailability of tryptophan central to the synthesis of the neurotransmitter serotonin. In this systematic review, we examine the relationship between kynurenine metabolites (kynurenine, kynurenic acid, tryptophan, quinolinic acid, the ratio of kynurenine and tryptophan) and mood disorders by conducting a meta-analysis. Fifty-six studies were identified, 21 met inclusion criteria and 14 were deemed suitable (9 investigating unipolar depression and 5 bipolar disorder). We found decreased levels of kynurenine in unipolar major depression vs. healthy controls but studies were significantly heterogeneous in nature. No significant differences were found in tryptophan levels or kynurenine/tryptophan ratios. Kynurenine metabolites are likely to play a role in major depression but an exact etiological role in mood disorder seem complex and requires further research.