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The aim of this systematic review was to assess if cadmium and lead levels are linked to anxiety and depression. A systematic literature search was conducted to identify observational trials evaluating the impact of cadmium and lead on the incidence and phenotype of depression and anxiety. The search identified 1059 records. Overall eighteen studies comprising 28,304 participants with a female predominance (n = 19,483; 69%) were included. Cadmium and lead levels were analyzed in eight and thirteen studies, respectively. Five studies found an association between blood cadmium levels and depression, among them three trials which reported that individuals in the highest quartile of blood cadmium had higher odds of showing depressive symptoms. Sex and smoking status were found to be potential confounders of cadmium impact on the depressive phenotype. None of the studies found association between the level of anxiety and blood cadmium levels. Nine studies demonstrated association between depressive symptoms and blood lead concentration. High lead levels may be associated with anxiety and neurobehavioral deficits. There are many factors that influence both the levels of cadmium and lead, and the severity of depression and anxiety in the respondents. There is no clear evidence for the impact of cadmium and lead levels on the development of depressive symptoms but a lot of indirect evidence points to this., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)