The purpose of the present study was to determine if acute responses in PGC-1α, VEGFA, SDHA, and GPD1–2 mRNA expression predict their associated chronic skeletal muscle molecular (SDH–GPD activity and substrate storage) and morphological (fibre-type composition and capillary density) adaptations following training. Skeletal muscle biopsies were collected from 14 recreationally active men (age: 22.0 ± 2.4 years) before (PRE) and 3 h after (3HR) the completion of an acute bout of sprint interval training (SIT) (eight 20-s intervals at ∼170% peak oxygen uptake work rate separated by 10 s of recovery). Participants then completed 6 weeks of SIT 4 times per week with additional biopsies after 2 (MID) and 6 (POST) weeks of training. Acute increases in PGC-1α mRNA strongly predicted increases in SDH activity (a marker of oxidative capacity) from PRE and MID to POST (PRE–POST: r = 0.81, r2 = 0.65, p < 0.01; MID–POST: r = 0.79, r2 = 0.62, p < 0.01) and glycogen content from MID to POST (r = 0.60, r2 = 0.36, p < 0.05). No other significant relationships were found between acute responses in PGC-1α, VEGFA, SDHA, and GPD1–2 mRNA expression and chronic adaptations to training. These results suggest that acute upregulation of PGC-1α mRNA relates to the magnitude of subsequent training-induced increases in oxidative capacity, but not other molecular and morphological chronic skeletal muscle adaptations. Additionally, acute mRNA responses in PGC-1α correlated with VEGFA, but not SDHA, suggesting a coordinated upregulation between PGC-1α and only some of its proposed targets in human skeletal muscle.