Background: Worldwide, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases and one of those producing greatest impact on patients’ day-to-day quality of life. Our study aim is to validate the “Living with Chronic Illness Scale” for a Spanish-speaking T2DM population.Methods: In this observational, international, cross-sectional study, 582 persons with T2DM were recruited in primary care and outpatient hospital consultations, in Spain and Colombia, during the period from May 2018 to June 2019. The properties analysed were feasibility/acceptability, internal consistency, reliability, precision and (structural) content-construct validity including confirmatory factor analysis (CFA). The COSMIN checklist was used to assess the methodological/psychometric quality of the instrument.Results: The scale had an adequate internal consistency and test retest reliability (Cronbach’s alpha = 0.90; intraclass correlation coefficient = 0.96, respectively). In addition, the instrument is precise (standard error of measurement = 3.34, with values <½SD = 8.52) and correlates positively with social support (DUFSS) (rs = 0.56), quality of life (WHOQOL) (rs = 0.51-0.30) and satisfaction (SLS-6) (rs = 0.50-0.38). The CFA supported the 5-domains structure, but a 23-item version showed better fit: CMIN/df= 3.11; goodness of fit index= 0.91; comparative fit index= 0.91 and root mean square error of approximation = 0.06 (90% confidence interval, 0.06-0.07). The COSMIN checklist is favourable for all the properties analysed, although weaknesses are detected for content validity.Conclusions: “Living with T2DM” (LW-T2DM) is a valid, reliable and accurate instrument for use in clinical practice to determine how a person’s life is affected by the presence of diabetes. This instrument correlates well with the associated constructs of social support, quality of life and satisfaction. Additional research is needed to determine how well the questionnaire structure performs when robust factor analysis methods are applied.