Purpose: To examine physiological responses to submaximal field running with changes of direction (COD), and to compare two approaches to assess running economy (RE) with COD, ie, during square=-wave (SW) and incremental (INC) exercises. Methods: Ten male team=-sport athletes performed, in straight=-line or over 20 m shuttles, one maximal INC and four submaximal SW (45, 60, 75 and 90% of the velocity associated with maximal pulmonary O-2 uptake [vVO(2p)max]). Pulmonary (VO2p) and gastrocnemius (VO2m) O-2 uptake were computed for all tests. For both running mode, RE was estimated as the O-2 cost per kilogram of bodyweight, per meter of running during all SW and INC. Results: Compared with straight=-line runs, shuttle runs were associated with higher VO2p (eg, 33 +/- 6 vs 37 +/- 5 mL O-2.min(-1).kg(-1) at 60%, P < .01) and VO2m (eg, 1.1 +/- 0.5 vs 1.3 +/- 0.8 mL O-2.min(-1).100 g(-1) at 60%, P =.18, Cohen's d = 0.32). With COD, RE was impaired during SW (0.26 +/- 0.02 vs 0.24 +/- 0.03 mL O-2.kg(-1).m(-1), P < .01) and INC (0.23 +/- 0.04 vs 0.16 +/- 0.03 mL O-2.kg(-1).m(-1), P < .001). For both SW and INC tests, the changes in RE with COD were related to height (eg, r = .56 [90% CL, 0.01; 0.85] for SW) and weekly training/competitive volume (eg, r = -0.58 [-0.86;-0.04] for SW). For both running modes, RE calculated from INC was better than that from SW (both P < .001). Conclusion: Although RE is impaired during field running with COD, team=-sport players of shorter stature and/or presenting greater training/competitive volumes may present a lower RE deterioration with COD. Present results do not support the use of INC to assess RE in the field, irrespective of running mode.