This study aimed to examine the effects of cold exposure, hypoxia, and fatigue on pistol marksmanship and target engagement in trained marksmen. Twelve healthy subjects (mean6SD age: 28.864.0 years) performed 3 testing visits under normal/normoxic [Norm21] (24° C; 21% FiO2), cold/normoxic [Cold21] (10° C; 21% FiO2), and cold/hypoxic [Cold14] (10° C; FiO2: 14.3) conditions. Pistol marksmanship and target engagement were assessed through draw time (DT) and shoot-no-shoot (SNS) courses of fire. The 2 protocols were performed before (TpreF) and immediately after (TpostF) a sandbag deadlift fatiguing protocol. Significance was set at p, 0.05. Significant condition 3 time interactions (p 5 0.01-0.03) were found for accuracy SNS (SNSacc), misses SNS (SNSmiss), and total shots SNS (SNStot). Follow-up analyses indicated that SNSacc increased by 14.3% (p 5 0.03), SNSmiss decreased by 34.7% (p 5 0.02), and SNStot decreased by 10.6% (p 5 0.04) from TpreF to TpostF during the Cold21 condition alone. No significance was found for these in the Norm21 (p50.08-0.22) or Cold14 (p50.18-0.47) conditions. Total time (SNST) to completion of the SNS (p50.09) and DT (p50.14) showed no significance across time or condition. Significant difference across time for Cold14 (p50.03-0.02) for reaction time was found. Exercise likely resulted in increased thermogenesis that improved tactically relevant motor skills including SNSacc, decreased SNSmiss, and SNStot in Cold21, but not Cold14. The additive effect of hypoxia coupled with exercise in the Cold14 condition did not improve tactical performance, suggesting multi-stressor environments result in competing physiological responses. Tactical strength and conditioning specialists as well as operators should aim to improve thermoregulation during Cold21 conditions, with exercise as a possible intervention. [ABSTRACT FROM AUTHOR]