Inflammatory processes are putative mechanisms underlying chronic disease. In this study we explore linear and non-linear associations between personality and change in inflammatory markers (C–reactive protein [CRP], fibrinogen, and white blood cell count [WBC]). In total, 5294 older adults (Mage = 64.51 ± 8.34 years) provided blood samples in 2008 with 3751 providing follow-up samples four year later. Midway between the two assessments, participants completed a measure of personality. After controlling for participant demographics (e.g., age, gender) and health-related lifestyle factors (e.g., exercise, cigarette smoking), we found that higher levels of agreeableness and lower levels of conscientiousness were associated with higher CRP levels, and (for conscientiousness) an increase in CRP over time. Age moderation effects indicated that agreeableness and conscientiousness were related to WBC among older participants in the sample (over ~ 70 years of age). These findings provide evidence that agreeableness and conscientiousness traits are important for inflammatory biomarkers in older adulthood.