Little is known about the spectrum or frequency of comorbidities in patients with chronic lymphocytic leukemia (CLL). We investigated the prevalence and prognostic implications of comorbidities in patients with newly diagnosed CLL. Local/non-referred patients with CLL evaluated by a hematologist at Mayo Clinic within 1 year of diagnosis were eligible for this retrospective review. Of 1195 individuals evaluated for newly-diagnosed CLL between 1995 and 2006, 373 (31%) were local/non-referred. At diagnosis, 89% of these patients had one or more comorbidities, and 46% had at least one major comorbidity. Twenty-six percent of patients failed to meet NCI working group guidelines to participate in a clinical trial. On multi-factor analysis, Rai risk category (1.39 per each risk category increase; p < 0.0001) and age (1.056 per year increase; p < 0.0001) were the only factors associated with overall survival. We conclude that, although common, comorbid conditions are less important than age and stage in predicting prognosis in newly diagnosed patients with CLL. Clinical trials evaluating treatments that are designed to be tolerated by patients who do not meet traditional clinical trial eligibility criteria are needed.