Objective: Certain personality traits have been associated with increased risk of chronic systemic inflammation. Since the expression of personality traits differs by sex, this factor may also influence the associations between personality and inflammation. The objective of this study was to investigate the association between the five dimensions of personality and high-sensitivity interleukin-6 (IL6) in a healthy population, and to determine whether these relationships were different in men and women. Methods: IL6 was measured in 91 medically healthy participants, and per-sonality was assessed using the Five-Factor Model (FFM) of personality. Physical activity was also measured using the International Physical Activity Questionnaire (IPAQ), since physical activity is known to influence inflammation. Multivariable regression models were estimated for each sex, including personality domains and level of physical activity, controlling for age and body mass index (BMI). Results: Higher ratings in the dimension of Openness to Experience predicted higherIL6 values in men only, after adjusting for age and BMI, variables known to affect inflammation (p < 0.05). Similarly in women only, higher Agreeableness predicted lower IL6 levels. Level of physical activity did not predict IL6 in either sex. Conclusion: Relationships between IL6 and personality traits exist in both men and women, but the nature of these associations differs by sex. These associations appear to be independent of other factors including physical activity. The findings raise the possibility that certain personality domains may make people more vulnerable to, or more protected from, conditions usually associated with pathological, chronic systemic inflammation.