Background: SARS-CoV-2 has caused a high mortality in institutionalised individuals. There are very few studies on the involvement and the real impact of COVID-19 in nursing homes. This study analysed factors related to morbidity and mortality of COVID-19 in institutionalised elderly people. Methods: This cohort study included 842 individuals from 12 nursing homes in Sant Cugat del Vallès (Spain) from 15 March to 15 May 2020. We evaluated individual factors (demographic, dependence, clinical, and therapeutic) and those related to the nursing homes (size and staff) associated with infection and mortality by SARS-CoV-2. Infection was diagnosed by molecular biology test. Results: Of the 842 residents included in the analysis, 784 underwent a Polymerase Chain Reaction (PCR) test; 74.2% were women, the mean age was 87.1 years, and 11.1% died. The PCR test was positive in 44%. A total of 33.4% of the residents presented symptoms compatible with COVID-19 and of these, 80.9% were PCR-positive for SARS-CoV-2. Infection by SARS-CoV-2 among residents was associated with the rate of staff infected in the homes. Mortality by SARS-CoV-2 was related to male sex and a greater grade of dependence measured with the Barthel index. Conclusions: SARS-Cov-2 infection in institutionalised people is associated with the infection rate in nursing home workers and mortality by SARS-Cov-2 with sex and greater dependency according to the Barthel index. Adequate management of nursing home staff and special attention to measures of infection control, especially of individuals with greater dependence, are keys for successful management of future pandemic situations.