Ultrasonic vocalizations (USVs) in neonatal mice provide a means of modeling communication deficits in neurodevelopmental disorders. Mature mice deficient in SAP90/PSD95-associated protein 3 (SAPAP3) display compulsive grooming and anxiety-like behavior, conditions that are often associated with neurodevelopmental disorders. To date, however, aspects of neurodevelopment have not been investigated in SAPAP3-deficient mice. Here, we examined whether neonatal SAPAP3-deficient mice display altered USVs. We recorded USVs from 5-day-old sapap3 and sapap3 mice, and also monitored developmental reflexes in these mice during the early postnatal period. Sapap3 mice display an increase in the number and duration of USV calls relative to sapap3 littermates, despite otherwise similar developmental profiles. Thus, SAPAP3, previously well-characterized for its role in compulsive grooming, also plays a heretofore unidentified role in neonatal communication. Aberrant social communication and compulsive behavior are core symptoms of autism spectrum disorders, and these results show that SAPAP3-deficient mice may serve to model some aspects of these conditions.