Abstract: Objective To investigate the effects of different administration periods of ondansetron combined with dexamethasone on intraoperative and postoperative nausea and vomiting in cesarean section, as well as neonatal outcomes.Methods A total of 148 parturients, aged 18-45 years, with American Society of Anesthesiologists (ASA) grades Ⅱ—Ⅲ and body mass index (BMI) of 18-35 kg/m² who underwent elective cesarean section under spinal anesthesia from April 2024 to February 2025 were enrolled. According to the random number table method, they were divided into two groups (n=74): a pre-anesthesia administration group (group A) and a post-umbilical cord clamping administration group (group B). Group A received intravenous ondansetron (4 mg) and dexamethasone (4 mg) 30 min before spinal anesthesia, while group B received the same regimen immediately after umbilical cord clamping. The incidence and severity of nausea and vomiting were recorded during the following time intervals: from initiation of anesthesia to fetal delivery (T₁), from fetal delivery to completion of uterine suturing (T₂), from completion of uterine suturing to skin closure (T₃), from the end of surgery to 2 h postoperatively (T₄), from 2 to 6 h postoperatively (T₅), and from 6 to 24 h postoperatively (T₆). Umbilical arterial blood gas analysis was performed after delivery, and neonatal Apgar scores at 1 min and 5 min were recorded. Maternal heart rate (HR), mean arterial pressure (MAP), oxygen saturation (SpO₂), and adverse events were also documented.Results Compared with group B, group A showed a significantly reduced incidence of nausea and vomiting during T₁ and T₂ (24.32% vs 10.81%, P=0.031; 39.19% vs 17.57%, P=0.004), along with significantly decreased nausea and vomiting scores (P=0.031 and P=0.007, respectively). No significant differences were observed between the two groups during T₃-T₆ (P>0.05). There were no statistically significant differences between the two groups in neonatal body weight and umbilical arterial blood gas parameters, Apgar scores, maternal vital signs, or incidence of adverse events (P>0.05).Conclusions Prophylactic administration of ondansetron combined with dexamethasone before spinal anesthesia significantly reduces the incidence of early intraoperative nausea and vomiting during cesarean section without adversely affecting neonatal outcomes, demonstrating good safety.