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.