Purpose: To inform high-quality rehabilitation services, this study investigates if patients with glioma located in the right- or left-hemisphere present with different health-related quality of life, symptomatology, and functional performance in the early disease state. Material and methods: Between 2013 and 2017, 81 adult patients were assessed during the first week of chemo-radiation, following resection. Patients were stratified into two groups depending on a right- or left-hemispheric lesion. Independent t-tests analyzed potential differences regarding health-related quality of life, symptomatology, and functional performance. Results: Forty-five patients (56%) had a tumor located in the right hemisphere, whereas 36 patients (44%) had a tumor in the left hemisphere. Except for more patients with tumors in the left hemisphere having their tumor located in eloquent brain areas, the groups were well matched. No group differences were found in health-related quality of life. Group differences were found in communication deficits (Δ-10.9, 95%CI -19.1; -2.3, p = 0.01), which were more frequent in patients with left-sided lesions, and of headaches (Δ13.9, 95%CI 1.8; 25.9, p = 0.02), which were more frequent in patients with right-hemispheric lesions, who also had significantly greater difficulties with process-skills when performing everyday life tasks (Δ-0.3, 95%CI -0.5; -0.1, p < 0.01). Also, weak evidence suggests that patients with Glioblastoma Multiforme located in the right hemisphere are more affected by fatigue compared to their left-hemispheric comparisons (Δ14.6, 95%CI 0.19; 29.0, p < 0.05). Conclusions The hemispheric location of a glial-cell brain tumor has no consequence for health-related quality of life at the beginning of chemo-radiation treatments. However, findings of tumor-location dependent conditions of communication, headache, patients' ability to perform executive functions, and fatigue should be considered in rehabilitation situations when designing an intervention to potentially improve executive functions and relieve the symptoms. Implications for rehabilitation It is unclear if laterality impact glioma patients health-related quality of life and functional performance, which might implicate differentiated rehabilitation interventions. The hemispheric location of a glial-cell brain tumor has no consequence for the health-related quality of life at the beginning of chemo-radiation, following surgery. Tumor-location dependent conditions of communication, headache, fatigue, and patients' ability to perform executive functions should be considered when designing an intervention to improve executive functions and symptom-relieve. In rehabilitation interventions, tumor laterality is not a factor that needs to be considered before recommending aerobic training to improve the functional capacity of patients with glioma.