Objective. To elucidate the association among circulating IL-8 and total mortality in a cohort of elderly, and to explore potential sex differences in the observed association. Methods. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) is a cohort of 70-year-old men and women living in Uppsala, Sweden; baseline period: 2001-2004. IL-8 serum measurements were performed in 1003 participants. Results. In total, 61 men and 40 women died during follow-up (median 7.9 years). Baseline IL-8 concentrations were higher in women than in men (P = 0.03). In a multivariable model adjusting for age, established cardiovascular risk factors, and C-reactive protein, log-transformed standard deviation increments in IL-8 levels were weakly associated with an increased risk for total mortality (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.02-1.23, P < 0.05) in the whole cohort. Stratified analysis revealed an association in women (HR 1.18, 95% CI 1.06-1.30, P < 0.01) but not in men (HR 0.98, 95% CI 0.76-1.26). Conclusions. A weak association between IL-8 serum levels and an increased risk for mortality was observed. The prospective data support the role of IL-8 as a biomarker of interest; yet, further studies are warranted to elucidate validity of our finding and the possibility of a sex difference.