Exercise and meditation improve health and well-being, potentially through decreasing systemic inflammation. In this study, healthy adults (N = 413) were randomized to 8 weeks of training in aerobic exercise, matched mindfulness-based stress reduction, or wait-list control. Three inflammation-related biomarkers (C-reactive protein, interleukin-6, and interferon-gamma-inducible protein-10) were assessed preintervention, directly postintervention, and 17 weeks later. Within-group analyses found that exercise participants had decreased serum interferon-gamma-inducible protein-10 postintervention and 17 weeks later, whereas C-reactive protein was lower in mindfulness-based stress-reduction participants 17 weeks postintervention only. Self-reported physical activity or amount of meditation practice did not predict biomarker changes. This study suggests that (a) training in aerobic exercise can lower interferon-gamma-inducible protein-10, a chemokine associated with interferon activity and illness, and (b) training in mindfulness meditation may have a delayed effect on C-reactive protein, an important inflammatory biomarker. The findings highlight the likelihood of multiple, distinct pathways underlying the health-promoting effects of these lifestyle interventions.