Stressful life events may accelerate aspects of immune aging, but habitual use of an adaptive emotion regulation strategy, cognitive reappraisal, may attenuate these effects. This study examined whether cognitive reappraisal moderates the associations between life stressor frequency and stressor desirability on aspects of immune aging, including late-differentiated CD8+ T and natural killer (NK) cells and inflammatory markers (IL-6, TNF-α, and CRP), both between and within people in a longitudinal sample of 149 older adults (mean age = 77.8, range: 64–92 years). Participants reported stressful life events, use of cognitive reappraisal, and provided blood semiannually for up to 5 years to assess aspects of immune aging. Multilevel models, adjusted for demographic and health covariates, tested the between-person (stable, trait-like differences) and within-person associations (dynamic fluctuations) among life stressors and reappraisal on immune aging. Experiencing more frequent life stressors than usual was associated with higher levels of late-differentiated NK cells within person, but this effect was accounted for by experiencing health-related stressors. Unexpectedly, experiencing more frequent and less desirable stressors were associated with lower average levels of TNF-α. As expected, reappraisal moderated the associations between life stressors and late-differentiated NK cells between people and IL-6 within people. Specifically, older adults who experienced less desirable stressors but also used more reappraisal had significantly lower proportions of late-differentiated NK cells on average and lower levels of IL-6 within-person. These results suggest cognitive reappraisal may play a protective role in attenuating the effects of stressful life events on aspects of innate immune aging in older adults.