Social support is understood as a protective factor for mental health and emotional well-being, especially at school. The Multidimensional Scale of Perceived Social Support (MSPSS) is one of the most widely used tools worldwide to assess this construct. The main purpose of the present study was to validate the scores of the MSPSS in a large sample of non-clinical adolescents. The sample consisted of 2,235 compulsory secondary education students in Spain ( = 14.49, = 1.76, age range 12-18 years, 52% female) obtained by stratified random sampling. The model, consisting of three interrelated factors, showed the most adequate goodness-of-fit indices. The results support the measurement invariance of the MSPSS across sex, age, and sexual orientation. McDonald's omega reliability indices between .862-.934 were obtained. MSPSS scores were significantly and negatively associated with emotional and behavioral problems, depression, and suicidal behavior, and positively associated with life satisfaction. The MSPSS is a reliable instrument to assess social support through self-report in school settings. In this regard, assessing social support using this tool is particularly useful in programs promoting well-being or preventing mental health disorders.