Malaria accounts for a considerable amount of Morbidity and mortality with children bearing the greatest burden. The study aimed to investigate the haematological alterations in children infected by Plasmodium falciparum (P. falciparum) species. A case control study with a total of ninety-five microscopically confirmed P. falciparum malaria infected children and fifty apparently healthy age and gender matched controls from Enugu State University Teaching Hospital, Parklane, Wesley Specialist Hospital and Akpugo Community Health Centre, Enugu were recruited for the study. Haematologic parameters were estimated using five part differential automated analyzer (Mindray BC 5300) with ethylene-diamine-tetra-acetic-acid anticoagulated blood. The result of P. falciparum infected male children revealed significant decrease (p < 0.05) in haematocrit (32.76 + 4.82)%, haemoglobin (10.34 + 1.46) g/dl, white blood cell (3.65 + 2.81)x109/L, neutrophil (20.41 + 15.16)% and platelet (228.41 + 113.51) x109/L, compared to the controls; haematocrit (35.60 + 2.70)%, haemoglobin (11.27 + 0.90) g/dl; white blood cell (7.97 + 2.55)x109/L, neutrophil (30.33 + 8.04)% and platelet (315.45 + 53.64) x 109/L. It also showed a significant increase (p < 0.05) in monocyte (3.28 + 2.63)%, basophil (1.68 + 1.15)% compared to the controls; monocyte (1.89 + 1.10)%, basophil (0.44 + 0.46)%. The results of P. falciparum infected female children revealed significant decrease (p < 0.05) in white blood cell (4.93 + 2.95)x109/L, neutrophil (19.61 + 15.14)%, mean corpuscular haemoglobin (23.58 + 2.37)pg, mean corpuscular volume (74.67 + 8.00)fl, and platelet (257.00 + 129.55) x109/L compared to the controls; white blood cell (6.70 + 1.75) x109/L, neutrophil (26.91 + 7.97)%, mean corpuscular haemoglobin (25.12 + 1.96)pg, mean corpuscular volume (79.13 + 5.37) fl and platelet (303.13 + 54.02) x109/L, significantly increased (p < 0.05) monocyte (3.38 + 2.78)%, basophil (2.19 + 1.36)% as compared to the controls; monocyte (1.85 + 0.82)%, basophil (0.48 + 0.45)%. However, P. falciparum infected male children showed to be more anaemic compared to the infected females. Indeed, Plasmodium falciparum malaria infection in children has great impact on the haematologic parameters, thus its investigations serves as competent measures of differential diagnosis.