The General Comfort Questionnaire (GCQ), developed by Katharine Kolcaba, has not been validated in any speaking Spanish country, subsequent validation is necessary. To translate the General Comfort Questionnaire (GCQ) in English language into Spanish (S-GCQ) and to examine the psychometric properties of the S-GCQ. Validation was performed on a randomly selected sample of 600 nurses from eight Valencia and Murcia public hospitals. This study analyzed the psychometric properties and factor structure using translation and back-translation of the original version, Principal Component Analysis (PCA), Confirmatory Factor Analysis (CFA), Internal Consistency (IC) and Multidimensional Scaling (MS). The instrument showed excellent internal consistency (Cronbach’s alpha of 0.90), good item-total correlation, and a coefficient of determination of 0.94 in multidimensional scaling. Factor analysis supported the twelve-factor structure reflecting dimensions of the original instrument. The S-GCQ is a valid and reliable Spanish-language assessment instrument to measure nurses’ comfort. It would be appropriate to validate the S-GCQ instrument for assessing nurses’ comfort in Primary Care and other health settings.