Background: Assessment of patients prior to cytotoxic chemotherapy usually includes absolute neutrophils count. Other cellular markers of susceptibility to infection as well as immunocompetence include the T Helper lymphocyte count. In cancer patients, decrease in these lymphocytes has been observed to be associated with decreased overall survival. Aim: To assess the degree of CD4 lymphopenia encountered during cytotoxic chemotherapeutic treatment for cancer and evaluate the differences observed for the various drug combinations. Subjects and Methods: Eighty patients with various histologically diagnosed malignancies had their CD4 lymphocyte counts carried out at days 0 and 12 of the first cycle of their various chemotherapeutic regimens. They were adult patients who had been diagnosed with breast cancer 36/80 cases (45%), nonâHodgkin’s lymphoma 8/80 cases (10%), Hodgkin’s lymphoma 13/80 cases (16.3%), multiple myeloma 7/80 cases (8.8%), colorectal carcinoma 6/80 cases (7.5%), and other malignancies 10/80 cases (12.5%). CD4 lymphocyte count was done using the Partec Cyflow® 2000 CD4 cell counter, and their socioâdemographic data of the patients were assessed using a questionnaire. Results: The mean (sd) CD4 lymphocyte count preâ and postâchemotherapy was observed to be 567 (341) cells/μLand 349 (207) cells/μL while the median values were 454 cells/μLand 349 cells/μL respectively. There were significant differences in CD4 lymphocyte counts after chemotherapy compared to the preâchemotherapy values. Conclusion: Epirubicin combinations used in breast cancer patients as well as (Adriamycin, Bleomycin, Vinblastine, Dacarbazine) ABVD regimen used in treatment of Hodgkin’s lymphoma were found to be significantly less lymphotoxic than other chemotherapeutic combinations. These drugs or their combinations may be less immunotoxic than other known regimen used for these malignancies.