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“Sickness behavior” is an orchestrated suite of symptoms that commonly occur in the context of inflammation, and is characterized by changes in affect, social experience, and behavior. However, recent evidence suggests that inflammation may not always produce the same set of sickness behavior (e.g., fatigue, anhedonia, and social withdrawal). Rather, inflammation may be linked with different behavior across contexts and/or across in- dividuals, though research in this area is under-developed to-date. In the present study (n = 30), we evaluated the influence of affective context and individual differences in difficulty detecting bodily sensations (i.e., interoceptive difficulty) on social perception following an inflammatory challenge. Inflammation was induced using the influenza vaccine and inflammatory reactivity was operationalized as changes in circulating levels of interleukin-6 (IL-6) before the vaccine and approximately 24 h later. Twenty-four hours after administration of the influenza vaccine, we manipulated affective context using a well-validated affect misattribution task in which participants made trustworthiness judgments of individuals with neutral facial expressions following the rapid presentation of “prime” images that were positive or negative in affective content. Interoceptive difficulty was measured at baseline using a validated self-report measure. Results revealed significant interactions between inflammatory reactivity to the influenza vaccine and affective context on social perception. Specifically, in- dividuals with greater inflammatory reactivity were more biased by affective context when judging the trust- worthiness of neutral faces. In addition, interoceptive difficulty and affective context interacted to predict social perception such that individuals with greater interoceptive difficulty were more biased by affective context in these judgments. In sum, we provide some of the first evidence that inflammation may amplify the saliency of affective cues during social decision making. Our findings also replicate prior work linking interoceptive ability to the use of affect-as-information during social perception, but in the novel context of inflammation.