Objectives: Investigating the hazardous effect of Phototherapy on Platelet counts in healthy neonates with Neonatal hyperbilirubinemia (NH). Study Design: Cross Sectional study. Setting: Department of Paediatrics, SMBB Medical College Layari General Hospital, Karachi, Sindh. Period: January 2018 to May 2019. Material & Methods: A sample of 313 neonates suffering from NH was selected according to the inclusion and exclusion criteria. Blood Platelets were counted at baseline, and 24, 48 and 72 hours of phototherapy. Statistical software SPSS 21.0 (IBM, Incorp, USA) was used for data analysis using paired t-test and Pearson`s Chi- square test at P≤0.05. Results: Platelet counts at 24, 48 and 72 hours of phototherapy were found 2.97±0.45×109/L, 3.38±0.48×109/L and 3.52± 0.47×109/L respectively. Platelet counts at 24, 48 and 72 hours showed statistically significant difference compared to baseline counts (P<0.05). A statistically insignificant decline in total population platelet count after phototherapy was noted (P>0.05). However, thrombocytopenia was noted in 9 (2.87%) cases; comprising mild and moderate in 7 (2.23%) and 2 (0.64%) cases respectively. Conclusion: The present study observed thrombocytopenia in 9 (2.87%) of total cases; of which mild and moderate thrombocytopenia occurred in 7 (2.23%) and 2 (0.64%) cases respectively.