A recent meta-synthesis study with a sample of >12 million participants revealed that the male advantage in mental rotation (MR) is the largest cognitive sex/gender difference found in psychological literature. MR requires test takers to mentally rotate three-dimensional cubic figures under time restrictions. Previous studies have investigated how biological and social factors contribute to cognitive sex/gender differences in tasks of this type. Spatial anxiety and self-confidence in MR tasks have received less attention. The present study investigated the contribution of these psychological factors to sex/gender differences in MR performance. Participants (n = 269) completed two MR tasks that differed in task difficulty. Participants also indicated their self-confidence (for each item) and spatial anxiety. The results revealed that pronounced sex/gender differences in spatial anxiety and self-confidence mediate sex/gender in MR performance, especially when task demands are high. The current findings suggest that task-irrelevant factors that are not spatial cognitive in nature contribute largely to the well-known medium to large sex/gender differences in MR. Future studies should further explore mechanisms underlying cognitive sex/gender differences within a biopsychosocial approach.