Background: Jaundice is one of the most common problems that affect newborns in the first few days of life. Approximately 60% of full-term and 80% of the preterm newborn may develop neonatal jaundice. Although neonatal jaundice is of physiological type in most of these cases, some cases may have elevated serum bilirubin levels which, if not treated, may lead to bilirubin encephalopathy and subsequently bilirubin induced neurological dysfunction (BIND). Objective: This study aimed to evaluate the effect of intensive phototherapy on B and T cells by measuring the percentages of CD19+, CD4+ and CD8+ lymphocytes subsets in newborns after 72 hours from exposure to intensive phototherapy to evaluate its effect on the immune system. Patients and methods: A prospective cohort study carried out in Zagazig University Hospital, Pediatric Neonatal Intensive Care Unit (NICU) and Clinical Pathology Departments. The study included 50 full-term newborns. Results: There was no significant difference regarding CD4, CD8 and CD19 for the patient group. Furthermore, the study showed that the percentages of CD4+ and CD8+ lymphocytes subsets showed no change in newborns after 72 hours of exposure to phototherapy, but CD19+ was highly significantly lower before treatment only. In addition, the follow up of those 25 jaundiced newborns for occurrence and frequency of infection and need for hospitalization for a period of six months after discharge showed no effect. Conclusion: our results showed no effect of phototherapy on lymphocyte subsets after 72 hours of exposure and no effect on infant immunity.