Low birth weight is associated with both schizophrenia and neurocognitive impairment. Yet, to our knowledge, no previous study has examined the relationship between lower birth weight and neurocognitive deficits in schizophrenia spectrum disorders (SSD). In this preliminary study, we investigated the relationship using a broad neuropsychological battery in cases with SSD and matched control subjects. The sample consisted of all subjects in the Developmental Insult and Brain Anomaly in Schizophrenia study, a nested case-control investigation developed from a large birth cohort, which followed subjects longitudinally. Case ascertainment was based on computerized record linkages between the birth cohort members and the Kaiser Permanente Medical Care Plan, and all diagnoses were confirmed by consensus diagnosis following the Diagnostic Interview for Genetic Studies. Lower birth weight was associated with impairment in executive function, working memory, generalized intellectual function, and neuromotor function in cases with SSD but not in control subjects. No deficits were observed in verbal memory for either group. These results support the hypothesis that lower birth weight plays a role in neuropsychological disruptions in SSD and that the antecedents of lower birth weight may have a greater impact on these disruptions in SSD than in controls. These data may facilitate a better understanding of the etiopathogenesis of the cognitive underpinnings of SSD.