Introduction The aim was to evaluate two biomarker scores trained to identify comorbidity burden in the prediction of specified chronic morbidities, and mortality in the general population. Methods Cardiovascular biomarkers were measured in the cardiovascular cohort of the Malmö Diet and Cancer Study. A score of 19 biomarkers associated with Charlson Comorbidity Index (CCI) was created (BSMDC). Individuals with CCI diagnoses and other major comorbidities were excluded. Another score of 11 biomarkers associated with comorbidity burden from a previous study of acute dyspnea was also created (BSADYS). The scores were prospectively evaluated for prediction of mortality, and some chronic diseases, using Cox Proportional Hazards Model. Results Fully adjusted models showed that BSMDC was significantly associated per 1 SD increment of the score with incident COPD, 55%, and congestive heart failure, 32%; and with mortality, 33% cardiovascular, 91% respiratory, 30% cancer, and 45% with all-cause mortality. The BSADYS showed no association with these outcomes, after simultaneous inclusion of both biomarker scores to all the clinical covariates. Conclusion BSMDC shows strong prediction of morbidity and mortality in individuals free from comorbidities at baseline, and the results suggest that healthy individuals with high level of BSMDC would benefit from intense preventive actions.