Infectious mononucleosis (IM) or Mononucleosis syndrome is caused by an acute infection of Epstein-Barr virus (EBV). This study was aimed at determining the levels of haemoglobin, total white blood cell (TWBC) count, neutrophils, lymphocytes, monocytes and eosinophils in patients infected with infectious mononucleosis at Federal Teaching Hospital, Owerri. A total of sixty subjects (30 patients and 30 controls) were enrolled in the study after giving their informed consent and completing questionnaires. The procedure was carried out at Federal Teaching Hospital, Owerri. Five millilitres of venous blood sample was collected at the ante-cubital vein aseptically and was dispensed into ethylenediaminetetraacetic acid (EDTA) containers. The EDTA containers were properly labeled with the subject’s name, sample number and date of collection. Haemoglobin was determined using the cyanmethaemoglobin method, TWBC was determined using the improved Neubauer counting chamber, while the differential count was determined using Romanowsky staining method. Data generated were analyzed using SPSS version 27, and mean, standard deviation, t-test, correlation and p-value were determined. The mean values of haemoglobin (8.9±1.44)g/dl and neutrophils (28.53±12.77)%, were significantly reduced in patients with infectious mononucleosis when compared to the controls (12.83±1.34)g/dl and (54.27±10.20 ((p=0.000 and p=0.001)) The mean values of TWBC (17.66±8.54)%, lymphocytes (59.87±13.14)% and monocytes (10.30±6.68)%)% were significantly increased in patients with infectious mononucleosis when compared to the controls (6.17±2.53)%, (49.23±13.57)% and (5.93±2.91)% ) respectively (p=0.000, p=0.003 and p=0.002). There was no significant difference in the mean value of eosinophil count in infectious mononucleosis (1.30±1.56)% (p=0.784) when compared to the controls (1.20±1.24)%. There were no significant differences in the mean values of haemoglobin, TWBC, neutrophil, lymphocyte, monocyte and eosinophil counts in male patients with infectious mononucleosis (9.14±1.52)g/dl, (19.16±9.36)x109/L, (27.69±11.18)%, (59.44±11.17), (10.13±6.12)% and (1.44±1.89)% when compared to the female patients (8.82±1.38)g/dl, (15.94±7.46)x109/L, (29.50±14.38)%, (60.36±15.51)%, (10.50±7.50)% and (1.14±1.09)% (p=0.568, p=0.311, p=0.705, p=0.852, p=0.881 and p=0.614). There was a non-significant positive correlation of haemoglobin with TWBC, neutrophils, lymphocytes, monocytes and eosinophils in infectious mononucleosis patients (r=0.17, p=0.357; r=0.15, p=0.421, r=0.07, p=0.730, r=0.11, p=0.563 and r=0.06, p=0.751). In conclusion, the data in the present study showed that infectious mononucleosis is characterized by increase in lymphocytes and monocytes with decreased levels of haemoglobin and neutrophils. Haemoglobin concentration does not have any relationship with white blood cells in patients with infectious mononucleosis. In the management and treatment of patients with infectious mononucleosis, complete blood count should be incorporated as a routine test, so as to aid in the diagnosis.