Patients with obsessive-compulsive disorder (OCD) have increased rates of neurological soft signs (NSS) when compared to healthy controls. However, previous findings have been confounded by the presence of co-morbidity with disorders themselves associated with increased NSS, such as schizophrenia. Moreover, it remains unclear whether NSS in OCD reflect a vulnerability to this disorder. This study aimed to examine: 1) the severity of NSS in patients with OCD alone, in patients with OCD and co-morbid psychosis (schizophrenia or bipolar disorders), and in healthy controls; and b) whether unaffected first-degree relatives of patients with OCD also demonstrate a higher prevalence rate of NSS than healthy controls. NSS were assessed with the Cambridge Neurological Inventory (CNI) in 100 patients with OCD, 38 patients with OCD and psychosis (22 with bipolar disorders and 16 with schizophrenia), and 101 healthy controls. Forty-seven unaffected first-degree relatives of patients with OCD only were also administered the CNI. Patients with OCD showed significantly higher scores in motor coordination and total NSS than controls, and patients with OCD co-morbid with psychosis also showed significantly higher scores in motor coordination and total NSS than controls. Although there were no differences in NSS between patients with OCD only and OCD and psychosis as a whole, patients with OCD co-morbid with schizophrenia showed significantly higher scores in motor coordination than patients with OCD, patients with OCD and bipolar disorder, and healthy controls. Unaffected first-degree relatives only showed a higher prevalence rate than healthy controls in specific motor coordination signs, such as Opposition and Extinction. These findings suggest that patients with OCD exhibit more NSS than healthy controls, and that motor coordination signs may be even more extensive when OCD is co-morbid with psychosis. Some of these abnormalities may be indicative of a vulnerability to these disorders, as indicated by their presence in un-affected first-degree relatives.