Quality of life (QOL) is an important issue in patients with amyotrophic lateral sclerosis (ALS). QOL measurements can help the support care team understand how to maintain or improve QOL in ALS patients. The purpose of this study was to describe the relationship between health-related QOL, disease severity and social support in ALS patients. In the current study, 49 German ALS patients were evaluated using the European quality of life score (EQ-5D), ALS Functional Rating Scale in its revised form (ALSFRS-R), Social Support Questionnaire (F-SozU K-14) and the Beck depression inventory. Data concerning patient history and socioeconomic background were collected using a semi-structured interview. Age, gender, number of children, habitation, socioeconomic status and disease duration were not significantly related to health-related QOL (EQ-5D). Positive correlations were found between the ALSFRS-R, social support and health-related QOL, whereas depression was negatively correlated with the ALSFRS-R score. A multiple linear regression model indicated a significant influence of the ALSFRS-R score on health-related QOL in ALS patients, with an additional trend for social support as a predictor. These results suggest that because of the logarithmic association between measures, compensatory therapy for loss of health-related QOL should be optimised during the course of the disease in ALS patients.