Introduction and objective: Lithium and selenium have been the subjects of extensive research for many years. Concern about the physiological action of these elements results from the application of lithium in medicine, as well as the beneficial influence of selenium supplementation in different pathological states. However, little data are available concerning their effect on the homeostasis of essential microelements in organs. Therefore, the aim of the current study was to evaluate the influence of lithium and/or selenium administration on homeostasis of iron, zinc, copper and manganese in the liver of rats. Material and methods: The experiment was carried on 24 male Wistar rats (4 groups of 6 animals) subjected to the treatment with: group I (control) – saline; group II – lithium carbonate at a dose of 2.7 mg Li/kg b.w.; group III – sodium selenite at a dose of 0.5 mg Se/kg b.w.; group IV – both lithium carbonate and sodium selenite at the doses mentioned above. Administration was performed for 6 weeks, once a day by stomach tube, in the form of water solutions. Results: The tissue content of zinc, iron and manganese showed no statistical differences among the studied groups. Zn was slightly decreased in group III vs. control and group II. Fe was insignificantly enhanced in groups II and IV vs. control. Mn in group IV was slightly increased vs. groups II and III. Cu in group III was significantly decreased vs. group IV and slightly depleted vs. groups I and II. Conclusions: With the exception of Cu in the Se-treated group, lithium and/or selenium did not affect the studied microelements’ liver homeostasis in a significant way. These results may contribute to the knowledge of essential microelements homeostasis in human organisms undergoing lithium therapy, and/or selenium supplementation.