<p>Phototherapy is the standard treatment for neonatal hyperbilirubinemia. However, its impact on hematologic indices related to oxidative stress and systemic inflammation, particularly in preterm infants, remains insufficiently understood. In this retrospective observational study, 96 neonates who received phototherapy were evaluated. Hematologic ratios including red cell distribution width to platelet count (RDW/PLT), RDW to lymphocyte count (RDW/LF), and platelet distribution width to plateletcrit (PDW/PCT) were analyzed. Systemic inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory index (SI), systemic immune inflammation index (SIRI), and pan-inflammatory value (PIV) were also compared before and after treatment using Wilcoxon signed-rank tests. Phototherapy was associated with an increase in RDW/PLT from a median of 0.11 to 0.14 (<i>p</i> = 0.0007, 95% CI 0.02 to 0.05) and in RDW/LF from 2.98 to 3.62 (<i>p</i> = 0.0005, 95% CI 0.50 to 0.80), as well as a decrease in PDW/PCT from 42.1 to 36.4 (<i>p</i> = 0.0001, 95% CI − 8.0 to − 4.5). No significant changes were observed in systemic inflammatory markers (<i>p</i> greater than 0.05 for all). <i>Conclusion</i>: Phototherapy induces localized hematologic changes that may reflect oxidative activity, without provoking systemic inflammation. RDW/PLT and RDW/LF may serve as accessible indicators of oxidative response. These findings support the hematologic safety of phototherapy in term and near-term neonates, while further research is needed in extremely preterm infants due to their increased susceptibility.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> <p><b>What is Known:</b></p> <p>• <i>Phototherapy is an effective and widely used treatment for neonatal jaundice</i></p> <p>• <i>Experimental studies suggest that it may influence oxidative stress pathways</i></p> <p><b>What is New:</b></p> <p>• <i>This study demonstrates that phototherapy alters RDW-based hematologic ratios without activating systemic inflammation</i></p> <p>• <i>RDW/PLT may serve as a practical early marker of oxidative stress response in neonates, reinforcing the safety of phototherapy while raising questions for preterm care</i></p> </entry> </row> </tbody> </tgroup> </Table></p>