Low testosterone (T) is frequent in men with chronic illnesses. The clinical features of T deficiency (TD) overlap with those of chronic diseases. The aim of this study is to evaluate the relative contribution of chronic disease score (CDS) and low T to the presence of TD symptoms. A consecutive series of 3862 men (aged 52.1 ± 13.1 years) consulting for sexual dysfunction were studied. Several clinical and biochemical parameters were collected, including the structured interview, ANDROTEST, for the assessment of TD symptoms. Penile color Doppler ultrasound (PCDU) was also performed. Based on the medications taken, the CDS was calculated. For a subset of 1687 men, information on mortality was collected (follow-up of 4.3 ± 2.6 years). Higher CDS was associated with lower free and total T (TT) as well as with higher ANDROTEST score. When introducing CDS and TT in multivariable models adjusted for age, severe erectile dysfunction and impaired morning erections were associated with both CDS (odds ratio and 95% confidence interaval, OR [95% CI] = 1.25 [1.13; 1.37] and 1.38 [1.29; 1.48], respectively) and low TT (OR [95% CI] = 1.11 [1.00; 1.23] and 1.13 [1.06; 1.21], respectively). Similar results were obtained for PCDU parameters. Hypoactive sexual desire was associated with low TT (OR [95% CI] = 1.21 [1.13; 1.30]), whereas it was inversely related with CDS (OR [95% CI] = 0.91 [0.84; 0.97]). When considering mortality for major cardiovascular events, TT <8 nmol l-1, but not CDS, was a significant predictor (hazard ratio [95% CI] = 5.57 [1.51; 20.63]). Chronic illnesses are associated with an overt TD. Both chronic diseases and low T can be involved in determining symptoms present in subjects complaining for sexual dysfunction. This should be considered in the diagnostic workup for TD.