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Introduction: A recent study has shown that fever control during septic shock was associated with decreased vasopressor requirements and reduced mortality. Thus, fever control may improve vascular tone during critically illness. The aim of this study was to evaluate the effect of fever control on peripheral vascular reactivity, assessed by near-infrared spectroscopy (NIRS). Methods: We prospectively included patients admitted to the intensive care unit (ICU) during a 6-month period who presented with core temperature ≥ 38.3°C and in whom attending physician had decided for fever control. Thenar tissue oxygen saturation (StO2) and muscle tissue hemoglobin index (THI) were measured using a tissue spectrometer (InSpectra Model 325; Hutchinson Technology Inc., Hutchinson, MN, USA). A vaso-occlusive test was performed at baseline (T0) and then 1 hour (T1) and 4 hours (T2) after initiation of fever control by rapid inflation of a pneumatic cuff around the upper arm. The following variables were recorded: THI, the StO2 desaturation slope during the occlusion (dSlope, %/sec) and the StO2 upslope of the reperfusion phase following the ischemic period (ascSlope, %/sec). Muscle oxygen consumption (NIR VO2; arbitrary units) was calculated as the product of the inverse StO2 desaturation slope and the mean THI over the first minute of arterial occlusion. Results: Thirty-one patients were included (16 male gender; age 56 [50-66] years); median temperature on TO was 38.7 [38.4-39.0]°C and most of them (25/31) were cooled using pharmacological intervention (IV paracetamol). Temperature at T1 and T2 were 38.0 [37.7-38.3] and 37.5 [37.0-37.8]°C. Values of StO2, THI, nirVO2, dSlope and ascSlope did not significantly change over time. Also, similar StO2, THI, nirVO2, dSlope and ascSlope time course was found when we compared patients on vasopressors (n=13) to the others. Nevertheless, among patients on vasopressors, we observed a significant increase in the dSlope (from 1.85 ± 0.84%/sec at T0 to 2.23 ± 0.68%/sec at T2, p =0.02) and decrease in the ascSlope (from -0.20 ± 0.04%/sec at T0 to -0.28 ± 0.08%/sec at T2, p =0.002). Also, we found a trend toward an increased nirVO2 (from 122 ± 46 at T0 to 153 ± 57 at T2, p =0.11). Conclusions: Fever control was associated with an improvement in peripheral vascular reactivity in critically ill patients on vasopressor therapy.