The relationship between caffeine consumption and cardiovascular disease (CVD) is controversial. However, chronic inflammation is associated with elevated CVD risk. Acute stress reliably increases proinflammatory markers such as IL-1β. We examined the effect of caffeine administration on the inflammatory stress response in 26 males and 26 females (age 18-29 years) with a confirmed family history of hypertension. Daily caffeine consumers were included following an intensive health screening to confirm health status. Following confirmation of parental hypertension, participants completed a 3.5-hr lab session to examine inflammatory responses to a speech and mental arithmetic stressor either without (N=26) or with (N=26) 3.3 mg/kg orally-administered caffeine. Blood samples were collected immediately before stress (20 min post-caffeine administration) and 60 min post-stress. Women completed their lab session during the luteal phase of their menstrual cycle. There was a significant time effect for interleukin-10 (F = 19.212, p < 0.01). Regardless of treatment group or gender, IL-10 decreased between baseline and recovery. Tumor necrosis factor-alpha showed a significant time by caffeine effect (F = 7.862, p = 0.007). There was an increase in TNF-α at follow-up as compared to baseline for the caffeine treated group. There were no significant findings for Il-4 or IL-1β. Results suggest that caffeine administration under stress may minimally influence the inflammatory response.