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Objective Fasting prolongs rodent lifespans by 50%, and also improves survival after surgery in mice. It is less clear whether fasting has similar positive effects in humans. While it is not feasible to reproduce lifelong studies in people, it is possible to investigate fasting in humans by testing acute stress responses. In this pilot study we examined the effects of fasting on inflammatory reactivity to acute psychosocial stress. Methods Twenty-nine adults (58% male) were randomly assigned to an overnight fast, a three-day juice fast, or a non-fasting control condition. The overnight group fasted for 18 hours, the juice group ingested only water or juice for three days, and the control group ate normally. After fasting, participants were exposed to the Trier Social Stress Test (TSST). IL-6 was measured in plasma at −1, 30, and 120 minutes post-TSST. Results Plasma concentrations of IL-6 increased significantly in response to stress in all groups (time effect: F = 20.26; p 0.001 ), but IL-6 responses in both fasting groups were lower compared to controls (group by time interaction: F = 3.98; p = 0.05). Conclusions These findings indicate allow the cautious conclusion that fasting positively affects acute inflammatory responses to stress, which might indicate that previous work on fasting in rodent models can be translated to humans. Future studies will have to further address this affect and relate altered stress responses to development of long-term health.