Losing an only child is a devastating life event that a parent can experience and may lead to post-traumatic stress disorder (PTSD). Social support could buffer against the negative influence of this trauma, but the neural mechanism underlying this alleviation effect remains poorly understood. In this study, voxel-based morphometry was conducted on brain MRI of 220 Han Chinese adults who had lost their only child. We performed multiple regression analysis to investigate the associations between social support scores – along with PTSD diagnosis, age, sex, body mass index (BMI) – and brain grey matter (GM) volumes in these bereaved parents. For all trauma-exposed adults, social support-by-diagnosis interaction was significantly associated with medial prefrontal volume (multiple comparisons corrected P ˂ 0.05), where positive correlation was found in adults with PTSD but not in those without PTSD. Besides, PTSD diagnosis was associated with decreased GM volume in medial and middle frontal gyri (P ˂ 0.001, uncorrected); older age was associated with widespread GM volume deficits; male sex was associated with lower GM volume in rolandic operculum, insular, postcentral gyrus (corrected P ˂ 0.05), and lower GM in thalamus but greater GM in parahippocampus (P ˂ 0.001, uncorrected); higher BMI was associated with GM deficits in occipital gyrus (corrected P ˂ 0.05) and precuneus (P ˂ 0.001, uncorrected). In conclusions, social support modulates the association between PTSD diagnosis and medial frontal volume, which may play an important role in the emotional disturbance in PTSD development in adults who lost their only child.