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Human immunodeficiency virus (HIV) infection, HIV medications and type 2 diabetes mellitus adversely affects kidney function including erythropoiesis. However, studies evaluating the coexisting effects of these conditions on serum erythropoietin (EPO) levels and the hematological profile of those affected in southern Nigeria are scarce. In this study, 128 adults between the ages of 18 and 59 years were selected from designated health facilities in southern Nigeria. They were divided into four groups (n=32 persons per group). Fasting/random blood sugar (FBS/RBS) levels, complete blood count (CBC), glycated heamoglobin (HBA1C), serum levels of erythropoietin were determined using standard methods. Results show a significant increase (P < 0.05) in serum EPO and total red blood cell count (TRBC) in the HIV only group compared to other groups. The total white blood cell count (TWBC), platelets count and platelet/lymphocyte rato increased in the diabetic plus HIV group. The FBS/RBS and theHBA1C levels increased in the diabetic and diabetic plus HIV groups compared to others. Increased erythropoiesis, depicted by increased serum EPO and TRBC could be attributable to improved use of HIV medications and improved lifestyle among the HIV positive patients on treatment. Poorly controlled T2DM with resultant increased HBA1C levels in the diabetic and diabetic plus HIV groups was responsible for the increase in TWBC and platelet count, likely due to impaired immune function leading to sepsis in these groups.