Background: Prior studies show that sickness induces anxiety as rated by subjective reports but have not linked this to overt behavior in humans. This study investigates the expression of distress during experimental sickness, its relation to self-reported anxiety, and the moderating role of gender in the association between overt distress and self-rated anxiety. Methods: 21 participants (18-34 yrs, 10 women) were semi-randomly chosen from a placebo-controlled, double-blind, within-subject experiment, in which participants were intravenously injected with a bacterial endotoxin lipopolysaccharide (LPS, 0.8 ng/kg body weight) triggering a transient inflammatory reaction and an acute state of sickness. In the current study, we coded the participants’ expression of moans, sighs and deep breaths (overt distress) during sickness from the video recordings of the experiment and analyzed these parameters in relation to the state part of the State Trait Anxiety Inventory (Spielberger et al., 1979) that was collected during the experiment. Results: The frequency of overt distress increased strongly during experimental sickness (1-3h post-injection of LPS) compared to baseline. The level of overt distress was not related to subjective feelings of anxiety. No clear difference was found between men and women in the frequency of expressed distress during sickness. Interestingly however, there was an inverted relation between anxiety and the expression of distress in women, so that women who reported higher anxiety expressed less distress overtly (ß = -0.52, p = 0.018). Conclusions: Experimental sickness strongly induces an increase of moans, sighs and deep breaths, but these are not directly associated with the level of state anxiety reported. The results also suggest that moans, sighs and deep breaths might have a different function in men and women.