The sickness response consists of a set of evolutionary stable behaviors facilitating recovery. Animals increase their pain sensitivity during sickness, but this has not been shown in humans. The present study investigated how an experimentally induced sickness response affected pain sensitivity in humans. Fifty healthy subjects (half women) were injected with a low dose of LPS ( Escherichia coli , 0.6 ng/kg) or saline in a double-blinded procedure. Pain tests were conducted at different time points; pressure pain threshold (0 h and 1.5 h), heat- and cold pain thresholds, noxious heat (0 h and 3.5 h), and noxious cold (3.5 h). Blood was taken at 0, 1.5, 3.5 and 5 h for cytokine analysis. LPS injected participants had higher cytokine levels (TNF, IL-6, IL-10 and IL-8) and increased anxiety as compared to placebo (all p < .05). Whereas heat- and cold pain threshold remained unaffected, pressure pain thresholds were significantly lowered in the LPS group as compared to controls ( p < .01). Noxious heat was perceived as significantly more painful during endotoxemia ( p < .05), but noxious cold was not. We here demonstrate that a low-grade peripheral inflammation increases the pain sensitivity for some pain modalities. We believe that both the endogenous pain inhibitory pathway as well as individual immunological reactivity may be important mechanisms in sickness-induced pain sensitivity, with potential implications for chronic pain.