Objective. The aim of this study was to design and validate LupusCol, an instrument for the evaluation of health-related quality of life (HRQoL) in Colombian adult patients with SLE. Methods. Items and domains of the initial instrument were defined. Preliminary tests were made with the participation of patients. Validity and reliability tests of the administration method were conducted. Usability tests were applied to the version obtained in the previous phases to complete the validation process. Results. Following preliminary tests, six items and one domain were excluded and two new items were added to the instrument, producing a form with 44 questions and 7 domains, which was submitted for validity and reliability tests. Factor analysis excluded three items, obtaining a Pearson’s correlation (PC) for the criteria validity of −0, 48; a Cronbach’s α coefficient for internal consistency of 0, 96; an intraclass correlation coefficient (ICC) for personal test-retest–telephone of 0.96 and an ICC personal test-retest–personal of 0.96. For interrater concordance a PC of 0.8, an ICC of 0.77 and a Lin’s coefficient of 0.86 were found. Sensitivity to change was demonstrated through analysis of variance, obtaining significant indicators about the scale, demonstrating the instrument’s ability to detect changes in HRQoL. Conclusion. The design and validation process was completed successfully. The scale has significant values for validity, reliability and sensitivity to change in the studied population.