Introduction: Neonatal jaundice in the first week of life is a common problem in newborns. The most important intervention for infants with severe hyperbilirubinemia is to initiate phototherapy without delay. Although phototherapy is the standard treatment for neonatal hyperbilirubinemia, it may lead to potential side effects such as retinal degeneration, diarrhea, dehydration, and skin rash. Phototherapy treatment can affect the function of the immune system in newborns via alterations in cytokine production. Objectives: In our study we hypothized that phototherapy can affect the level of pro-inflammatory and anti-inflammatory cytokines. We choose interleukin 6 (pro-inflammatory) and interleukin 10 (anti-inflammatory) to study this effect because they are produced by keratinocytes. Subjects and methods: Forty term and near term jaundiced neonates were chosen to conduct the study; they presented with neonatal jaundice (NNJ) in the 1st week of life with body weight ranging from (2kg- 4kg). All of them were subjected to phototherapy for the management of NNJ. Interleukin [IL]-6 and Interleukin IL-10: (Before and after 72 hours of phototherapy Results: our study revealed an increase in serum level of IL6 after treatment with phototherapy. However no change was observed for IL 10 between basal values and treatment with statistically significant P value for IL-6 statistically insignificant for IL-10. Conclusions: Phototherapy used in the treatment of neonatal hyperbilirubinemia can affect the level of cytokines but as the previous studies were not homogenous so more studies are needed to be done to study the effect of phototherapy on serum cytokines concentration in the newborn.