Aim To assess the association between self-reported health (SRH) and mortality from all-causes, cardiovascular disease (CVD) and cancer, in adults 65 years and older in Spain. Methods We analysed data of 894 adults (504 women, 390 men) aged 65 years and above from two population-based studies, the EUREYE-Spain study and the Valencia Nutritional Survey (VNS). SRH was assessed at baseline using a single question which is widely used in epidemiological studies: “Overall, how would you consider your health at present?” and the response options were: 1. Very good, 2. Good, 3. Fair, 4. Poor, 5. Very poor. Deaths were ascertained during a 12-year follow-up period, and we used Cox proportional hazards regression models to obtain adjusted hazard ratios (HR). Results During the 12 years of follow-up (8566.2 person-years), we observed 400 deaths, 158 (39.5%) due to CVD and 89 (22.3%) due to cancer. Fair and poor/very poor SRH were significantly associated with higher all-cause mortality after 12-years of follow-up, HR = 1.29 (95% CI, 1.03–1.61) and HR 1.53 (95% CI, 1.09–2.15), respectively. We observed evidence of higher CVD mortality among those who reported fair and poor/very poor SRH, although the association was attenuated and lost statistical significance in the fully adjusted models. Conclusion This study suggests that a poor SRH status is associated with a higher all-cause mortality risk among older adults in Spain. Checking SHR status may be useful to plan health care in older adults.