Background Paraoxonase-1 (PON-1) is an enzyme with a glycoprotein structure that depends on calcium and which is located in serum high-density lipoprotein (HDL). The aim of this study was to evaluate PON-1, and oxidant/antioxidant state, before and after treatment for neonatal sepsis, and to determine the usability of PON-1 in neonatal sepsis treatment. Methods A total of 35 neonatal sepsis patients and 35 healthy controls were included in the study. Activity of PON-1, total oxidant state (TOS) and total antioxidant state (TAS) were measured and oxidative stress index (OSI) was calculated. Results In the neonatal sepsis patients, pre-treatment TAS, TOS and OSI were significantly higher than the post-treatment levels (P < 0.0001, P < 0.0001 and P < 0.0001, respectively), and PON-1 was significantly lower (P < 0.0001). Similarly, pre-treatment TAS, TOS and OSI in the sepsis group were also significantly higher than in the control group (P < 0.0001, P < 0.0001 and P < 0.0001, respectively) and PON-1 was significantly lower (P < 0.0001). Post-treatment TAS in the sepsis group was significantly higher than in the control group (P = 0.009), whereas post-treatment TOS, OSI and PON-1 in the sepsis group were not significantly different to the control group (P = 0.078, P = 0.597 and P = 0.086, respectively). Conclusion Low serum PON-1 was found in neonatal sepsis. Serum PON-1 is thought to be a useful biomarker to evaluate the effectiveness of treatment and recovery in neonatal sepsis.