We investigated whether subclinical inflammatory markers high-sensitivity C-reactive protein (CRP) and fibrinogen are related to measures of physical functioning in mid-life women. Our sample included 543 participants in the Michigan site of Study of Women's Health Across the Nation (SWAN). Predictors included CRP from serum and fibrinogen from plasma. Performance-based outcomes included measures of gait, hand grip strength, flexibility, stair climb, 40-foot walk, and chair rise. Perception of physical functioning was assessed with the Medical Outcomes Study Short-Form 36 questionnaire. Regression analyses adjusted for relevant covariates. Cross-sectional associations were identified between higher CRP and more time spent in double support (with both feet on the floor while walking), shorter forward reach, slower 2-lb lift, and slower stair climb. Higher CRP and fibrinogen were associated with worse perceived functioning in cross-sectional analyses. Predictive associations across time were found between higher CRP and increased time spent in double support, diminishing forward reach distance and grip strength and worse perceived physical functioning. Predictive associations across time were also found between higher fibrinogen and greater time spent in double support, slower stair climb and worse perceived physical functioning. Our results suggest that inflammatory processes are associated with poor physical functioning in mid-life women. © 2009 Elsevier Inc. All rights reserved.