Abstract : Viral infection and immunological changes could affect the common pathophysiological presentations of Plasmodium infection. This work was therefore designed to determine pattern of viral seromarkers and evidence adaptive immune response in patients infected with Plasmodium spp. in Nigeria. 150 Plasmodium infected patients aged 9-72 years who have not initiated treatment and 100 age matched nonPlasmodium infected subjects were recruited and studied as test and control subject respectively. Parasite density was determined using standard method while Ag-Ab HIV, Anti-HCV, HBsAg, Plasma IgM and IgG were determined in all the subjects serologically by ELISA. The result obtained showed sero-viral status of 3.3% (2) anti-HCV, 16.7% (15) HBsAg and 0% Ag-AbHIV including no evidence of viral confection with another virus. There was a significant decrease in the IgM plasma value in the test subjects with increase in Plasmodium parasitemia with p<0.05. There was a significant increase in IgG in the test subjects with increase in Plasmodium parasetemia with p<0.05. There was also a significantly higher plasma IgM and IgG in the test subjects than the control subjects with p<0.05. The frequency of Plasmodium infection also decreased with increase in parasite density. This work revealed viral seromarker of 3.3% (2) anti-HCV, 16.7% (15) HBsAg and 0% Ag-Ab HIV including evidence of adaptive immune response manifested by significant increase in IgG and decrease in IgM with increase in Plasmodium parasitemia while the frequency of Plasmodium infection decreases with increase in parasite density