Introduction: Preventive care practices are a challenge in community care. This study examined hantavirus preventive practices and their relationship with personal and social factors, lifestyle, and cultural beliefs. Method: An explanatory sequential mixed methods design, guided by Leininger’s Theory of Culture Care Diversity and Universality, was used in two phases: (a) a cross-sectional relational design ( n = 109) and (b) ethnonursing research ( n = 30), in an endemic community in Panama. Univariate and bivariate analyses were used to analyze the quantitative data, whereas the Leininger’s analysis model was used to analyze the qualitative data. Results: In the quantitative phase, the most frequent preventive practice was household hygiene, and the least frequent was vector control. Two of the eight preventive practices were associated with personal factors and two were associated with social factors. In the qualitative phase, lifestyle, beliefs, and context were found to influence the adoption of hantavirus preventive practices and help explain the quantitative findings. Discussion: Knowledge and understanding of the social and cultural contexts are essential for hantavirus prevention.