Purpose: This experiment was designed to quantify the independent and combined influences of hyperthermia and dehydration on effector control during rest and exercise. Methods: To achieve that, whole-body hydration of healthy adults (N = 8) was manipulated into each of three states (euhydrated, 3% and 5% dehydrated), and then clamped within each of two thermal states (normothermia [mean body temperature: 36.1 °C] and moderate hyperthermia [mean body temperature: 38.2 °C]). Those treatment combinations provided six levels of physiological strain, with resting physiological data collected at each level. The effects of isothermal, thermally unclamped and incremental exercise were then investigated in normothermic individuals during each level of hydration. Results: At rest, dehydration alone reduced urine flows by 83% (3% dehydrated) and 93% (5% dehydrated), while the reduction accompanying euhydrated hyperthermia was 86%. The sensitivities of renal water conservation to 3% dehydration (−21% mOsm−1 kg H2O−1) and moderate hyperthermia (−40% °C−1) were independent and powerful. Evidence was found for different renal mechanisms governing water conservation between those treatments. Cutaneous vasomotor and central cardiac responses were unresponsive to dehydration, but highly sensitive to passive thermal stress. Dehydration did not impair either whole-body or regional sweating during rest or exercise, and not even during incremental cycling to volitional exhaustion. Conclusion: In all instances, the physiological impact of these thermal- and hydration-state stresses was independently expressed, with no evidence of interactive influences. Renal water-conservation was independently and powerfully modified, exposing possible between-treatment differences in sodium reabsorption.