Mercury is a heavy metal that can cause a variety of toxic effects on the organism, such as hematological and immunological alterations. In the present investigation, deleterious effects of mercury-intoxication in mice and a possible protective effect of diphenyl diselenide (PhSe)(2) were studied. Male adult Swiss albino mice received daily a pretreatment with (PhSe)(2) (15.6 mg/kg, orally) for 1 week. After this week, mice received daily mercuric chloride (1 mg/kg, subcutaneously) for 2 weeks. A number of hematological (erythrocytes, leukocytes, platelets, hemoglobin, hematocrit, reticulocytes, and leukocytes differential) and immunological (immunoglobulin G and M plasma concentration) parameters were evaluated. Another biomarker of tissue damage, lactate dehydrogenase (LDH), was also determined. The results demonstrated that mercury exposure caused a reduction in the erythrocyte, hematocrit, hemoglobin, leukocyte, and platelet counts and an increase in the reticulocyte percentages. (PhSe)(2) was effective in protecting against the reduction in hematocrit, hemoglobin, and leukocyte levels. (PhSe)(2) ameliorated reticulocyte percentages increased by mercury. However, (PhSe)(2) was partially effective in preventing against the decrease in erythrocyte and platelet counts. Immunoglobulin G and M concentrations and LDH activity were increased by mercury exposure, and (PhSe)(2) was effective in protecting against these effects. In conclusion, (PhSe)(2) was effective in protecting against hematological and immunological alterations induced by mercury in mice.