Background: Malaria parasitemia is a disease caused by Plasmodium parasites transmitted through the bite of an infected female anopheles mosquito. It continues to be a major public health concern worldwide, with a significant impact on morbidity and mortality, particularly in tropical and subtropical regions. Objective: The purpose of this study was to assess the levels of protein, red cell and platelet indices in patients infected with malaria parasitaemia in Owerri, Imo state. Method: This was a cross-sectional study carried out at federal university teaching hospital (FUTH) Owerri, Imo State, Nigeria. A total of hundred (100) individuals were enrolled in the study: 50 patients of ages 15years and above, who consented to be part of the research, and fifty (50) age-matched apparently healthy subjects who served as the controls. Blood Samples were collected aseptically, and were analyzed using standard laboratory methods. Results: The mean values of MCV (77.12±6.62)fl, MCH (24.46±3.15)pg, MCHC (28.83±1.25)g/dl, PLT(126.08±36.8)x109/L, MPV(7.82±0.95)fl, PCT/(0.13±0.12)%, PDW/(10.79±0.76)%, and total protein (5.54±0.46)g/dl were significantly reduced in subjects with malaria parasitaemia when compared to the healthy controls (89.92±5.06)fl, (30.43±1.73)pg, (33.22±1.61)g/dl,(33.22±1.61) x 109/L,(236.10±48.73)fl, (10.33±1.71)%, (0.23±0.01)%, (7.78±0.83)g/dl, (p =0.000, p= 0.000, p=0.000, p=0.001, p=0.000, p=0.001, p=0.000, p=0.000, while there was no significant difference in the mean value of RDW 13.38±2.13(g/dl) in subjects with malaria parasitaemia when compared to the healthy controls (13.91±1.28)g/dl (p = 0.309). Conclusion: This study has shown that malaria parasitaemia alters the levels of MCV, MCH, MCHC, PLT, MPV, PCT, PDW and Total protein, but has no effect on RDW. Therefore, total protein, red cell and platelet indices should be considered in the clinical assessment of patients with suspected or confirmed malaria parasitemia.