BACKGROUND: Evidence suggests that selenium (Se) supplementation could be useful as an adjunctive therapy to levothyroxine (LT₄) in the treatment of Hashimoto's thyroiditis (HT). To summarize evidence regarding its effect on thyroid autoantibodies' titers, demands in LT₄ replacement therapy, ultrasonographic thyroid morphology, and mood in patients with HT under LT₄ treatment, a systematic review and meta-analysis of relevant literature were performed.METHODS: Systematic review of prospective studies involving patients with HT under LT₄ treatment and meta-analysis of studies on randomized, placebo-controlled, blinded trials were performed.RESULTS: Patients with HT assigned to Se supplementation for 3 months demonstrated significantly lower thyroid peroxidase autoantibodies (TPOab) titers (four studies, random effects weighted mean difference: −271.09, 95% confidence interval: −421.98 to −120.19, p< 10⁻⁴) and a significantly higher chance of reporting an improvement in well-being and/or mood (three studies, random effects risk ratio: 2.79, 95% confidence interval: 1.21-6.47, p= 0.016) when compared with controls. Demands in LT₄ replacement therapy and ultrasonographic thyroid morphology were found either unaltered or underreported.CONCLUSIONS: On the basis of the best available evidence, Se supplementation is associated with a significant decrease in TPOab titers at 3 months and with improvement in mood and/or general well-being. Evidence suggests a different pattern of response to Se supplementation in HT relative to baseline TPOab titers, and this, if confirmed, could be used to identify which patients would benefit most from treatment. An improvement in thyroid function and morphology should be demonstrated before Se routine supplementation can be recommended in the treatment of HT.