Obsessive Compulsive Disorder (OCD) is characterized by hyperactivity in a network of forebrain structures, including the anterior cingulate cortex (ACC). Convergent evidence suggests that glutamatergic dysfunction may contribute to the disorder. Skin picking disorder (SPD) was listed as one of the obsessive-compulsive and related disorders, which is often comorbid with OCD and share overlapping phenomenology and pathophysiology. However, potential confounding effects between the two diagnostic effects on neurotransmitter levels remain largely unexamined. We examined the pregenual anterior cingulate cortex (pACC) glutamate and other neurochemicals in 62 subjects using a single-voxel acquisition 1H MRS at 3Tesla; of these, 47 subjects yielded usable measurements of both glutamate and glutamine and were included in the analysis (17 medicated with OCD alone, 13 medicated with comorbid OCD + SPD, 17 healthy control). OCD with comorbid SPD showed significantly lower pACC glutamate than in patients without SPD (p = 0.001) or control subjects (p = 0.035). OCD without SPD subjects showed pACC glutamate levels indistinguishable from controls (p = 0.501). In the OCD with SPD subjects, glutamate was correlated with Y-BOCS total score in female patients (n = 9, r = 0.69, p = 0.041). The main limitation of the study was the cross-sectional data. Our patients were on SSRI medication which may have modified the effect of SPD and OCD interaction on glutamate activity. Our results suggest that alterations of the glutamatergic system may play an important role in the pathophysiology of a subgroup of OCD and reduced pACC glutamate may be a biomarker of a distinct subset of OCD patients. Copyright © 2020. Published by Elsevier B.V.