Dysregulated brain glucose metabolism and lactate accumulation are seen following traumatic brain injury (TBI). The underlying molecular mechanism is poorly understood. Pyruvate dehydrogenase (PDH), the rate-limiting enzyme coupling cytosolic glycolysis to mitochondrial citric acid cycle, plays a critical role in maintaining homeostasis of brain glucose metabolism. PDH activity is maintained by the expression of its E1alpha1 subunit 1 (PDHE1alpha1) and is inhibited by the phosphorylation of PDHE1alpha1 (p-PDHE1alpha1). We hypothesized that PDHE1alpha1 expression and phosphorylation was altered in rat brain following controlled cortical impact (CCI)-induced TBI. Compared to naïve controls (=100%), PDHE1alpha1 protein decreased significantly ipsilateral to CCI (62%, P<0.05; 75%, P<0.05; 57%, P<0.05; and 39%, P<0.01) and contralateral to CCI (77%, 78%, 78% and 36% P<0.01) at 4h, 24h, 3- and 7-day post-CCI, respectively. PDHE1alpha1 protein phosphorylation level also decreased significantly ipsilateral to CCI (31%, P<0.01; 102%, P>0.05; 64%, P<0.05; and 14%, P<0.01) and to contralateral CCI (35%, 74%, P<0.05; 60%, P<0.05; 20%, P<0.01) at 4h, 24h, 3- and 7-day post-CCI, respectively. Similar reduction in PDHE1alpha1 and p-PDHE1alpha1 protein was found in the craniotomy (sham CCI) group. TBI-induced change in PDHE1alpha1 expression and phosphorylation could alter brain PDH activity and glucose metabolism.