Evidence from numerous animal models shows that vagal activity regulates inflammatory responses by decreasing cytokine release. Heart rate variability (HRV) is a reliable index of cardiac vagal regulation and should be inversely related to levels of inflammatory markers. Inflammation is also regulated by sympathetic inputs, but only one previous paper controlled for this. In a larger and more representative sample, we sought to replicate those results and examine potential sex differences in the relationship between HRV and inflammatory markers. Using data from the MIDUS II study, we analyzed the relationship between 6 inflammatory markers and both HF-HRV and LF-HRV. After controlling for sympathetic effects measured by urinary norepinephrine as well as a host of other factors, LF-HRV was found to be inversely associated with fibrinogen, CRP and IL-6, while HF-HRV was inversely associated with fibrinogen and CRP. We did not observe consistent sex differences. These results support the existence of the vagal anti-inflammatory pathway and suggest that it has similar effects in men and women.