Eleven patients with bipolar depression were given doses of up to 18 g per day of triacetyluridine (TAU) over 6 weeks to test the effect of uridine on symptoms of depression via Montgomery-Asberg Depression Rating Scale (MADRS; Asberg, Montgomery, Perris, Schalling, & Sedvall, 1978) scores and on cellular bioenergetics using phosphorus magnetic resonance spectroscopic imaging (31P-MRSI). All patients and comparison participants (n = 9) completed baseline 31P-MRSI scans, and 9 patients completed posttherapy scans. The percentage changes for MADRS scores (Week 2, −23.8; Week 3, −34.9; Week 4, −42.5) and the time effects of TAU on MADRS scores (Week 2, z = −2.07, p = .039; Week 3, z = −4.28, p < .001; Week 4, z = −4.54, p < .001) may reflect TAU effects on early symptom improvement. TAU responders (patients who had a 50% or greater reduction in MADRS scores from baseline at any time) demonstrated a significant difference from nonresponders in pH changes from baseline (effect size = 150). These results suggest that TAU treatment may decrease symptoms of depression and improve mitochondrial functioning.