Physical function measures have gained increased importance in the evaluation of older persons. The presence of comorbidity is a major and growing issue in geriatrics. To evaluate the relationship between comorbidity and physical function in community-dwelling older persons. Data are from baseline evaluation of the ilSIRENTE study (n = 364). Physical performance was assessed using the Short Physical Performance Battery (SPPB) and the 4-meter walking test. Muscle strength was measured by hand-grip strength. Functional performance was assessed using Basic and Instrumental Activities of Daily Living (ADLs and IADLs, respectively). Comorbidity was defined as >or=3 clinical conditions. Analyses of covariance and linear regressions were performed to evaluate the relationship between comorbidity and physical function. The mean age of participants was 85.9 (SD = 4.9) years. About one third (37.4%) of participants reported >or=3 clinical conditions. Participants with comorbidity had significantly worse results in all the physical function tests. Participants with comorbidity had significantly lower adjusted results for the 4-meter walking test (0.444 m/s) and the SPPB score (6.131) compared to those without comorbidity (0.531 m/s and 7.221; all p = 0.001, respectively). Participants with comorbidity were more IADL-impaired (3.152) than participants without comorbidity (2.767; p = 0.04). No significant association of ADLs and hand-grip strength with comorbidity was reported. Similar strengths of association for the 4-meter walking test (per SD increase, beta = -0.280; p = 0.001) and the SPPB (per SD increase, beta = -0.285; p = 0.001) with comorbidity were reported. Physical function measures, especially walking speed and SPPB, are associated with comorbidity. Physical performance measures may improve the clinical evaluation of older persons.