The purpose of this study was to determine the effects of four weeks of interval training with concurrent creatine supplementation on cardiorespiratory fitness and endurance performance (maximal oxygen consumption (o2PEAK), time-to-exhaustion (o2PEAKTTE), ventilatory threshold (VT), and total work done (TWD)) in college-aged men. Forty-three recreationally active college-aged men (Age: 23.5 ± 4.8 yrs; o2PEAK: 43.9 ± 9.9 ml·kg·min−1) volunteered to participate in this double-blind, placebo-controlled study. Participants were randomly assigned to one of three groups: creatine (Cr-5g Cr plus 15g flavored dextrose; n = 16), placebo (PL-20g flavored dextrose; n = 17), or control (n = 10) groups. Each supplement group ingested the assigned supplement twice daily on training days only (10g/day, 5 days/week). Prior to and following supplementation, each participant performed a continuous maximal oxygen consumption test (o2PEAK) on a cycle ergometer (Corival Lode, Gronigen, the Netherlands), which was further used to establish o2PEAKTTE (seconds) and VT (l·min−1). Participants were further assessed for TWD (kJ), calculated from the total time (T; seconds) completed at a workload corresponding to 110% of their maximal power output (watt, W) determined from the maximal oxygen consumption test [TWD (kJ)= (T × W)/1000]. Following initial testing, a two week familiarization period of training and supplementing occurred. Baseline values were then measured and all participants in the Cr and PL groups engaged in four weeks of high-intensity interval training (HIIT) training on a cycle ergometer. Each training session consisted of 5 bouts of a 2:1 minute cycling work to rest ratio, introduced in an undulating progression starting at 80% o2PEAK power output and reaching 120%. Separate two-way ANOVAs (group [Cr vs. PL vs. CON] × time [Baseline- vs. Post-]) were used to identify any group by time interactions. A significant time × treatment interaction occurred for o2PEAK (p < 0.001) and o2PEAKTTE (p < 0.001). Post hoc analyses indicated no significant differences between groups. Both groups increased in o2PEAK (Cr: 7.5%; Pl: 9.6%) and o2PEAKTTE (Cr: 6.2%; PL: 7.4%) following four weeks of HIIT. A significant time × treatment interaction occurred for VT (p = 0.040). Post hoc analyses indicated improvements in only the Cr (p = 0.001; 16.4% increase) group over time. No changes were observed in TWD in any group over time. Both o2PEAK and o2PEAKTTE improved following four weeks of HIIT. Cr supplementation seemed to only have an effect on VT, since improvements were observed in the Cr group while there were no changes in the PL group. TWD did not change following HIIT or Cr supplementation. HIIT seems to be an effective and time-efficient way to improve maximal endurance performance. The addition of Cr seemed to improve VT, but did not increase TWD. Therefore, 10g of Cr per day for 5 days per week does not seem to further augment maximal oxygen consumption, greater than HIIT alone; however, Cr supplementation may improve submaximal exercise performance.