<b><i>Introduction:</i></b> Nursing homes for older adults have been hot spots for SARS-CoV-2 infections and mortality. Factors that facilitate COVID-19 outbreaks in these settings need to be assessed. <b><i>Methods:</i></b> A retrospective cross-sectional study of a cohort of residents and workers in nursing homes taking occasion of a point seroprevalence survey was done in the Community of Madrid. Factors related to outbreaks in these facilities were analyzed. <b><i>Results:</i></b> A total of 369 nursing homes for older adults, making a population of 23,756 residents and 20,795 staff members, were followed from July to December 2020. There were 54.2% SARS-CoV-2 IgG+ results in residents and in 32.2% of workers. Sixty-two nursing homes (16.8%) had an outbreak during the follow-up. Nursing homes with outbreaks had more residents than those without (median number of 81 [IQR, 74] vs. 50 [IQR, 56], <i>p</i> < 0.001). Seropositivity for SARS-CoV-2 was lower in facilities with versus without outbreaks, for residents (42.2% [IQR, 55.7] vs. 58.7% [IQR, 43.4], <i>p</i> = 0.002) and for workers (23.9% [IQR, 26.4] vs. 32.8% [IQR, 26.3], <i>p</i> = 0.01). For both residents and staff, the number of infections in outbreaks was larger in centers with lower, as compared with intermediate or high seroprevalence. The size of the facility did not correlate with the number of cases in the outbreak. Taking the incidence of cases in the community as a time-dependent variable (<i>p</i> = 0.03), a Cox analysis (HR [95% CI], <i>p</i>) showed that intermediate or high seroprevalence among residents in the facility was related to a reduction of 55% (0.45 [0.25–0.80], <i>p</i> = 0.007) and 78% (0.22 [0.10–0.48], <i>p</i> < 0.001) in the risk of outbreaks, respectively, as compared with low seroprevalence. Also, as compared with smaller, medium (1.91 [1.00–3.65], <i>p</i> = 0.05) or large centers (4.57 [2.38–8.75], <i>p</i> < 0.001) had more respective risk of outbreaks. <b><i>Conclusions:</i></b> The size of the facility and the seroprevalence among residents in nursing homes, and the incidence of infections in the community, are associated with the risk of outbreaks of COVID-19. Facilities with greater proportion of seropositives had smaller number of cases. Monitoring of immunity in nursing homes may help detect those at a greater risk of future cases.