Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia.