Commercial fishermen represent a particularly vulnerable group within the Blue Economy (BE), enduring hazardous working conditions, strenuous labor, prolonged exposure to extreme weather, and irregular sleep and nutritional patterns. The health of these invisible workers holds significant implications for the social, economic, and environmental dimensions of fisheries, as it directly influences productivity. Despite their importance, no public data are available on fishermen's cardiometabolic health and health behaviors in Rhode Island. However, sound evidence suggests elevated cardiometabolic risks, altered sleep patterns, and chronic stress in similar fishermen populations globally. This paper establishes a comprehensive research framework to examine commercial fishermen's cardiometabolic health, protective and risk factors, quality of life (QoL), lifestyle behaviors, and productivity. The overarching goal is to identify potential targets for intervention to improve commercial fishermen's health behaviors, QoL, and cardiovascular health. Following the STROBE guidelines, this framework includes methodological, societal, environmental, and economic aspects to guide the development of an exploratory study protocol. A two-phase mixed-methods study will be conducted. Phase 1 (qualitative) will hold two focus groups (n = 6-10 participants per group) and will inform Phase 2 (quantitative), where biomarkers, health factors and behaviors, QoL, and productivity of commercial fishermen (n = 59) will be gathered. Recruitment began in January 2024, and data collection will end in August 2024. The results of this study are expected to be published in 2025. A framework was developed considering the impact and implications of commercial fishermen's health-related behaviors on BE-based states, sustainable communities, and marine ecosystems. This protocol established a guideline-based, two-phase mixed-methods study to explore the cardiometabolic health, QoL, and productivity of commercial fishermen. Since better cardiovascular health is associated with lower risks of cardiovascular disease death and all-cause mortality, the findings will provide a situational screening and inform the development of tailored theory-based preventive behavioral interventions.