Patients diagnosed with primary brain tumors such as glioma experience psychological distress throughout the illness trajectory. Determining which patient characteristics are associated with more severe mood disturbance throughout the illness trajectory can help identify patients at risk and assist in developing targeted interventions based on these factors. Adult glioma patients were eligible for participation. Data collection tools included an investigator completed clinician assessment tool, patient completed demographic form and the Profile of mood states-short form. A multiple regression model was used to describe the relationship between the patient groups and clinical factors. The study enrolled 186 glioma patients of various tumor grades, who were categorized in three groups (newly diagnosed, on-treatment, follow-up) based on disease status at time of visit. Newly diagnosed patients experienced more total mood disturbance than all the other groups. Characteristics associated with more severe mood disturbance varied by patient group: newly diagnosed patients who were not on corticosteroids and were not married were more likely to have higher mood disturbance [R(2) = 0.27, F (2, 29) = 5.31, p < 0.02]. For those on treatment, the use of concomitant medications, having more than 1 recurrence and low income predicted higher mood disturbance [R(2) = 0.417, F (4, 67) = 11.98, p < 0.001]. For those not on active treatment, female sex, anti-depressant use and having a lower income was associated with higher mood disturbance [R(2) = 0.183, F (3, 55) = 4.11, p < 0.02]. Additionally, when compared to other cancer groups, glioma patients reported similar mood disturbance to those with breast cancer. Factors other than disease characteristics are associated with higher mood disturbance and vary according to current disease status. The use of concomitant medications, demographic factors, recurrence and income are associated with mood disturbance and interventions may need to be tailored to these underlying factors.