Purpose: The aim of this study was 2-fold: (1) to examine the relationships between psychophysiological responses and locomotor demands with variations in technical performance during 2v2 and 4v4 conditioned games and (2) to compare psychophysiological and locomotor responses among players exhibiting higher and lower technical performance levels during the conditioned games. Methods: Twenty-four male youth soccer players (16.3 ± 0.8 y old) participating at the trained/developmental level underwent monitoring for psychophysiological responses (including heart rate, rating of perceived exertion, and visual analog scale), locomotor demands (such as distance covered), and technical performance variables (including successful and unsuccessful passes and shots, as well as lost balls) across 2v2 and 4v4 formats. These formats were applied 4 times within a single session and were replicated twice over 2 weeks. Results: Large correlations between the number of lost balls per minute and mean heart rate were found in both the 2v2 and 4v4 games (r = .586 and r = .665, respectively). Successful shots were inversely and largely correlated with mean heart rate (r = −.518) in 4v4 games. The number of interceptions per minute was inversely and significantly correlated with the visual analog scale in 2v2 and 4v4 games (r = −.455 and r = −.710, respectively). The frequency of lost balls was significantly higher among players who attained a higher mean heart rate (2v2: +42.9%, P = .031, d = −0.965; 4v4: +57.1%, P < .001, d = −2.072). Conclusions: Coaches should be aware that highly psychophysiologically demanding scenarios may significantly impair technical performance. Therefore, prioritizing technical performance by deliberately adjusting the intensity should be considered.