New Findings: What is the central question of this study? Fire service instructors are frequently exposed to live fire scenarios, representing the most extreme chronic occupational heat exposure. These individuals report a series of unique health issues. We sought to identify whether the number of exposures completed was associated with inflammatory and immunological markers and symptoms of ill health. What is the main finding and its importance? Fire service instructors exhibit greater levels of inflammatory markers in comparison to firefighters. The number of exposures to fire is positively related to the prevalence of ill health and inflammation. Implementation of a proposed limit of nine exposures per month might be appropriate to minimize health issues. Abstract: Fire Service Instructors (FSIs) experience ∼10 times more fire exposures than firefighters (FFs), and the increased physiological stress from this potentially puts them at risk of ill health and future cardiac events. The aim of the study was to establish whether FSIs exhibit elevated biomarkers associated with cardiac event risk, identify whether FSIs experience systemic inflammation linked to the frequency of fire exposure and evaluate a proposed exposure limit of nine exposures per month. Blood samples were collected from 110 Fire Service personnel (mean ± SD, age,44 ± 7 years; height, 178.1 ± 7.1 cm; and body mass, 84.3 ± 12.0 kg; FSIs n = 53 and FFs n = 57) for biomarker analysis. Work history details were collected from all participants. Participants with biomarker concentrations above healthy reference ranges were classified as being ‘at risk’. The neutrophil-to-lymphocyte ratio, platelet count, cardiac troponin T, interleukin (IL)-6, IL-1β, C-reactive protein and immunoglobulin G were greater in FSIs than in FFs (P < 0.05). Multiple regression analysis revealed that 18.8% of IL-6, 24.9% of IL-1β, 29.2% of C-reactive protein and 10.9% of immunoglobulin G variance could be explained by the number of exposures to heat per month. Odds ratios revealed that those FSIs above the nine per month exposure limit were six to 12 times more likely to be classified as ‘at risk’ and were 16 times more likely to experience symptoms of ill health. Increased cytokine levels suggest that FSIs experience systemic inflammation, which is related to symptoms of ill health. We propose that an exposure limit could reduce the prevalence of these biomarker risk factors and ill health.