Introduction: Healthy lifestyles are relevant to several diseases and to maintain individuals' mental health. Exposure to epidemics and confinement have been consistently associated with psychological consequences, but changes on lifestyle behaviours remain under-researched. Materials and Methods: An online survey was conducted among the general population living in Spain during the COVID-19 home-isolation. In addition to demographic and clinical data, participants self-reported changes in seven lifestyle domains. The Short Multidimensional Inventory Lifestyle Evaluation was developed specifically to evaluate changes during the confinement (SMILE-C). Results: A total of 1254 individuals completed the survey over the first week of data collection. The internal consistency of the SMILE-C to assess lifestyles during confinement was shown (Cronbach's Alpha = 0.747). Most participants reported substantial changes on outdoor time (93.6%) and physical activity (70.2%). Moreover, about one third of subjects reported significant changes on stress management, social support, and restorative sleep. Several demographic and clinical factors were associated to lifestyle scores. In the multivariate model, those independently associated with a healthier lifestyle included substantial changes on stress management(p < 0.001), social support (p = 0.001) and outdoor time (p < 0.001), amongst others. In contrast, being an essential worker (p = 0.001), worse self-rated health (p < 0.001), a positive screening for depression/anxiety (p < 0.001), and substantial changes on diet/nutrition (p < 0.001) and sleep (p < 0.001) were all associated with poorer lifestyles. Conclusions: In this study, sizable proportions of participants reported meaningful changes in lifestyle behaviours during the COVID-19 pandemic in Spain. Moreover, the SMILE-C was sensitive to detect these changes and presented good initial psychometric properties. Further follow-up studies should collect relevant data to promote healthy lifestyles in pandemic times. (C) 2020 SEP y SEPB. Published by Elsevier Espana, S.L.U. All rights reserved.