Abstract: There has been high incidence of malaria and typhoid co-infection in Nigeria lately but no documented study has really considered its impact on the biochemical status of the patients. The aim of this study was to investigate the effect of malaria and malaria-typhoid co-infection on some hematological and biochemical parameters in infected patients. A total of 66 febrile patients and 10 apparently healthy persons from Bells University of Technology and Covenant University Health Centers, Ota, Ogun State were screened for the presence of plasmodium falciparum and salmonella typhi. Levels of Neutrophils, Lymphocytes, White Blood Cells, Packed Cell Volume (PCV), Albumin, Urea, Glucose, Total Bilirubin, Total Protein and Creatinine were estimated in the blood plasma of the study groups. A significant increase (p<0.05) in Creatinine, Urea and Total Bilirubin levels, Neutrophils and White Blood Cell counts were observed in both the malaria and co-infected patients as compared to the control. However, Albumin, Glucose, PCV, Lymphocytes and Total Protein levels were significantly reduced (p<0.05) in both the malaria and co-infected patients. This study indicates alterations in these parameters and therefore recommends proper monitoring during treatment in order to reverse them to normal levels.