The purpose of this longitudinal study was to compare the quality of life and affective state of patients receiving chemotherapy who developed oral mucositis to patients who did not. Outpatients had their mouths assessed at the beginning of their chemotherapy, completed the Multidimensional Quality of Life scale, Cancer version (MQOLS-CA) and the Profile of Mood States (POMS). Patients again completed the MQOLS-CA and POMS if they developed mucositis during their three cycles (monthly), or if they did not and were exiting the study. Seventy-seven outpatients completed the study; 28 patients developed mucositis and 49 did not. The MQOLS-CA total scores for the entire sample decreased significantly over time (F(1,75) = 25.44, P < 0.001), but there was no group by time interaction, i.e., the change in MQOLS-CA total scores did not depend on mucositis status. While the POMS Total Mood Disturbance scores for the entire sample increased significantly over time (F(1,75) = 19.55, P < 0.001), there was a significant group by time interaction (F(1,75)= 4.85, P = 0.03). Patients who developed mucositis had a significant increase in mood disturbance compared to patients who did not. Further, the POMS subscales of depression and anger showed the same pattern of significant increases. In conclusion, the development of mucositis adversely affected the outpatients' affective states, but not their QOL.