INTRODUCTION: Individuals with greater affect variability (i.e., moment-to-moment fluctuations possibly reflecting emotional dysregulation) are at risk for greater systemic inflammation, which is associated with cardiovascular disease. Some evidence suggests that affect variability is linked with poorer health indicators only among those with higher average levels of affect, particularly for positive affect (PA), and that associations may be non-linear. The present study sought to examine whether links between both PA and negative affect (NA) variability and inflammation are moderated by average level of affect. METHODS: Participants (N = 300, 50 % female, ages 21-70, 60 % non-Hispanic White, 19 % Hispanic, 15 % non-Hispanic Black) completed a lab assessment and provided a blood sample to measure systemic inflammation (i.e., TNF-α, IL-6, CRP). Affect was collected via a two-day ecological momentary assessment protocol where reports were collected about every 45-min during waking hours. Momentary affect ratings were averaged across both days (i.e., iM), separately for PA and NA, for each participant. Affect variability was calculated as the person-specific SD (i.e., iSD) of affect reports, separately for PA and NA. Linear and quadratic interactions were tested. Models included covariates for sex, race, and body mass index. RESULTS: There were significant interactions between NA iM and NA iSD predicting TNF-α (b = 6.54; p < 0.05) and between PA iM and PA iSD predicting IL-6 (b = 0.45; p < 0.05). Specifically, the association between these affect variability indicators and inflammatory markers were suggestive of a positive association among those with higher average affect but a negative association among those with lower average affect. There was no evidence of non-linear associations between affect and inflammation. DISCUSSION: Incorporating interactive effects between affect variability and average affect may be an important consideration in understanding affective-inflammatory associations.