Modern coffee processing generates a complex, co-localized mixture of respiratory hazards, such as carbon monoxide (CO), volatile α-diketones (principally diacetyl and 2,3-pentanedione), and bio-reactive coffee dust, that challenge single-agent risk paradigms. This systematic review synthesizes quantitative exposure data, exposure-response relationships, mechanistic plausibility, and control efficacy to characterize the occupational respiratory burden associated with simultaneous exposure to these agents. A systematic search of literature (in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses – PRISMA 2020) was conducted choosing eligible studies reported quantitative exposure metrics (CO in ppm, α-diketones in ppb, particulate matter in mg/m³) and respiratory health outcomes among coffee industry workers. Task-based monitoring identified grinding, flavoring, and packaging as peak emission events. Epidemiological findings included sentinel clusters of obliterative bronchiolitis, increased prevalence of obstructive spirometric abnormalities, and measurable forced expiratory volume (FEV₁) declines associated with cumulative α-diketone exposure; organic dust exposure correlated with chronic cough, dyspnea, and reduced FEV₁/forced vital capacity. Co-exposure to CO, α-diketones, and coffee dust in roasting, grinding, and packaging operations produces a substantive occupational respiratory risk profile, including both acute systemic hazards and chronic small-airway injury. Preventing occupational risk requires prioritizing engineering controls, task-specific ventilation design for peak emissions, and longitudinal exposure and health surveillance to define dose-response relationships for complex mixtures and to inform evidence-based occupational exposure limits. Med Pr Work Health Saf. 2026;77(3)