There is a need for more information on the quality of life (QoL) in patients undergoing chemotherapy. We wanted to investigate the perception of health status in colon cancer patients before, 3 and 6 months after chemotherapy. A secondary purpose was to assess the different perceptions of QoL between men and women during and after adjuvant or palliative therapy. We investigated 100 patients throughout chemotherapy for colon cancer. Data were collected through the SF-36 questionnaire. The score of all variables analyzed in the study group was lower than in the control group, which indicates a lower performance status, more marked in the female sex. Patients were then subdivided by the state of disease (localized or metastatic) and the variables, were evaluated before, 3 and 6 months after therapy. In patients treated with adjuvant treatment, there was a worsening of the performance status, followed by an increase after 6 months. We found that after 3 months of therapy, affected male patients perceived more limitations in carrying out their work, other daily activities and social relationships, owing to both their emotional state and their physical health. In metastatic patients the values of the eight variables decreased dramatically after 6 months, indicating a worsening of the QoL. In patients who received adjuvant treatment there was a certain worsening of the health status at 3 months, followed by a general improvement after 6 months. This improvement was not observed in patients undergoing palliative therapy. Several differences were observed between men and women in performance status after treatment.