Cardiovascular diseases are a health problem throughout the world, especially in people with diabetes. The identification of cardiovascular disease biomarkers can improve risk stratification. Sclerostin is a modulator of the Wnt/β-catenin signalling pathway in different tissues, and it has recently been linked to vascular biology. The current study aimed to evaluate the relationship between circulating sclerostin levels and cardiovascular and non-cardiovascular mortality in individuals with and without type 2 diabetes. We followed up a cohort of 130 participants (mean age 56.8 years; 48.5% females; 75 with type 2 diabetes; 46 with prevalent cardiovascular disease) in which serum sclerostin levels were measured at the baseline. Time to death (both of cardiovascular and non-cardiovascular causes) was assessed to establish the relationship between sclerostin and mortality. We found that serum sclerostin concentrations were significantly higher in patients with prevalent cardiovascular disease (p<0.001), and independently associated with cardiovascular mortality (p = 0.008), showing sclerostin to be a stronger predictor of mortality than other classical risk factors (area under the curve = 0.849 vs 0.823). The survival analysis showed that an increase of 10 pmol/L in the serum sclerostin level resulted in a 31% increase in cardiovascular mortality. However, no significant association was observed between sclerostin levels and non-cardiovascular mortality (p = 0.346). From these results, we conclude that high sclerostin levels are related to mortality due to cardiovascular causes. The clinical implication of these findings is based on the possible use of serum sclerostin as a new biomarker of cardiovascular mortality risk in order to establish preventive strategies.