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To determine the influence of a patent foramen ovale and fibroblast growth factor-21 on core temperature (Tc) responses in SCUBA divers. Additionally, we aimed to quantify the individual and combined influences of wetsuit thickness and anthropometric data on Tc changes during the dives. An experimental study comparing the Tc responses between divers with (n = 17) and without a patent foramen ovale (n = 14). A total of 31 divers participated in the study. Tc was measured pre- and post-dive in 17–18 °C sea water using a telemetric pill. Additionally, blood was drawn pre-dive and ~ 1–2 h post-dive for measurement of fibroblast growth factor-21. There was no influence of a patent foramen ovale on the Tc responses during SCUBA diving in either dive profile (p > 0.05). Additionally, there was no influence of SCUBA diving on fibroblast growth factor-21 concentrations (p > 0.05). The strongest positive and significant associations with the ∆ Tc/min were found when multiplying wetsuit thickness in millimeters by body mass (r2 = 0.3147, p = 0.0010), BMI (r2 = 0.3123, p = 0.0011), and body surface area (r2 = 0.2877, p = 0.0019). There was a significant, negative linear relationship between the body surface area to mass ratio and ∆ Tc/min (r2 = 0.2812, p = 0.0032). These data suggest that Tc regulation during recreational SCUBA diving can be facilitated in part by the appropriate choice of wetsuit thickness for a given set of anthropometric characteristics. [ABSTRACT FROM AUTHOR]