This study explored the effects of oxytocin on Compassion Focused Imagery (CFI), that is, imagining another “mind” being deeply compassionate to oneself, and the interaction of these effects with self-criticism and feeling socially safe with others. Forty-four healthy participants (29 men and 15 women) completed self-report measures of self-criticism, attachment style, and social safeness before taking part in a double-blind randomized placebo controlled study. They attended two imagery sessions, receiving oxytocin in one and a placebo in the other. Positive affect was measured before and after each imagery session, and “imagery experience” was assessed after each session. Overall, oxytocin increased the ease of imagining compassionate qualities but there were important individual differences in how CFI was experienced. Participants higher in self-criticism, lower in self-reassurance, social safeness, and attachment security had less positive experiences of CFI under oxytocin than placebo, indicating that the effects of oxytocin on affiliation may depend on attachment and self-evaluative styles.