Comorbid conditions are highly prevalent in chronic lymphocytic leukemia (CLL), nevertheless, detailed information on the association of specific comorbidities with CLL prognosis is missing. Using Danish, nation-wide registers, we followed consecutive patients from CLL-diagnosis in 1997-2018, until death or end of follow-up. Sub-grouping of comorbidities was defined using a modified Charlson comorbidity index. Patients were matched on sex, date of birth (±1 month), and region of residency with up to ten comparators from the general population. In total, 9170 patients with CLL were included in the study, with a median of 5.0 years of follow-up. All comorbid conditions studied were individually associated with increased mortality, and many also with increased cause-specific mortality, related or unrelated to CLL. Comorbidity correlated with increased mortality from infections and cardiovascular disease. CLL patients, particularly older, had a significant loss of lifetime compared with the general population. This study highlights a large subgroup of comorbid CLL patients with an unmet treatment-need and missing efficacy and safety data on treatment, who are under-prioritized in clinical trials. Also, studies assessing interventions that may provide better tolerability of treatment in older or comorbid patients, with cancer in general, and CLL in particular, are warranted.