Inflammation, particularly interleukin-6 (IL-6), is associated with chronic disease in older adults, but not all older adults have the same progression of poor health outcomes. Self-efficacy may play a role in buffering the inflammatory burden in chronic disease. To evaluate associations between self-efficacy and IL-6, 159 community-dwelling older adults ( N = 159, M_age = 82 years, SD = 6.3 years) with one or more chronic illnesses were recruited for this cross-sectional study. Sweat IL-6 was collected using a noninvasive sweat patch worn for 72 hrs. Multiple linear regression with bootstrapping showed a significant association between social coping self-efficacy and IL-6 (β = −0.534, p = .010) after adjustment for age, sex, race, body mass index, financial strain, chronic conditions, and social support. Although preliminary, this study creates a rationale to explore the self-efficacy inflammatory biomarker association further. Enhancing self-efficacy might be a viable nonpharmacological treatment to lower or slow the inflammatory burden in older adults.