Objective To determine the direct and indirect effects of function on clinical variables such as age, pain intensity, years of the disease, severity of symptoms, and depression in women with electrodiagnostic and clinical diagnosis of carpal tunnel syndrome (CTS). Design A cross-sectional study. Setting Patients from an urban hospital referred to a university clinic. Methods Two hundred and forty-four (n = 224) women with CTS were included. Demographic and clinical data, duration of symptoms, function, symptom's severity of the symptoms, pain intensity, and depression were self-reported collected. Correlation and path analysis with maximum likelihood estimation were conducted to assess the direct and indirect effect of hand function on pain, age, years with the disease, symptoms severity, and depression. Results Significant positive correlations between function and pain intensity, years with pain and symptoms severity were observed. The path analysis found direct effects from depression, symptoms severity, and years with pain to function (all, P < 0.01). Paths between function and depression on pain intensity (both, P < 0.01) were also observed. The amount of function explained by all predictors was 22%. The indirect effects in the path analysis revealed that function exerted an indirect effect from depression to pain intensity (B = 0.18; P < 0.01), and from symptoms severity to the intensity of pain (B = 0.10; P < 0.01). Overall, the amount of current pain intensity explained by all predictors in the model was R2 = 0.22. Conclusions Our study demonstrated that function mediates the relationship between depression and symptoms severity with pain intensity in women with CTS. Future longitudinal studies will help to determine the clinical implications of these findings