This study investigated the effects of mixed-method cooling during a short break between exercise bouts on thermoregulation and cycling time-trial (TT) performance in the heat. In a randomized crossover design, nine physically active men performed two 30-min cycling bouts that consisted of 25-min constant-paced cycling at 55% of maximal oxygen uptake followed by a 5-min TT in the heat (35 °C, 50% relative humidity). The two bouts were separated by a 15-min break. During the break, participants were assigned to a control trial (CON; 5 g kg−1 fluid ingestion at room temperature) or a mixed-method cooling trial (COOL; 5 g kg−1 ice slurry ingestion and cooling vest to cool the neck and torso). Physiological (rectal [Tre], forehead deep-tissue [Tdeep-head], mean skin [T‾sk], forehead skin [Thead], and neck skin [Tneck] temperatures, heart rate [HR], and skin blood flow [SkBF]) and perceptual data (ratings of perceived exertion [RPE], thermal comfort [TC], and thermal sensation [TS]) were measured. At the end of the 15-min break, Tdeep-head (−0.5 ± 0.2 °C, p < 0.001), T‾sk (−5.6 ± 3.1 °C, p = 0.001), Thead (−0.8 ± 0.4 °C, p = 0.001), Tneck (−9.8 ± 6.0 °C, p = 0.002), HR (−17 ± 6 bpm, p < 0.001), SkBF (−27.7 ± 13.9%, p = 0.002), TC (+2.6 ± 2.5, p = 0.024), and TS (−4.7 ± 2.5, p = 0.011) improved in COOL compared to CON. Reductions in T‾sk and Tneck were quickly lost (5 min) during the second exercise bout but Tdeep-head, Thead, and TS remained lower in COOL until the commencement of the second TT. Compared to CON, Tre (−0.2 ± 0.2 °C, p = 0.002) and RPE (−1.3 ± 0.9, p = 0.010) were lower in COOL during the second exercise bout. The reduction in mean power output at the second TT was attenuated in COOL (−13.9 ± 26.9 W) compared to CON (−29.3 ± 29.4 W; p = 0.015). In conclusion, the mixed-method cooling during a short break reduced physiological and perceptual strain and improved cycling TT performance.