To investigate effects of carnitine deprivation and methylxanthines on cardiac performance, 23 newborn pigs were given intravenous nutrition with [CARN +] or without carnitine [CARN −] and with [MX +] or without [MX−] caffeine administration. Echocardiographic [ECHO] measurements of intraventricular septum [dIVS]/posterior wall [dPW] excursion, fractional shortening [%FS], and left ventricular ejection fraction [LVEF]) were performed on days 1, 5 and 12. ECHO and blood sampling (gases, metabolites, total [TC] and free [FC] carnitine) were then undertaken at baseline; during hypoxia; and after reoxygenation. Heart tissues were collected for metabolites, acid-soluble total [ASTC] and free carnitine [ASFC]. Results: No effects of MX were seen. Carnitine levels were lower in CARN− than CARN+ piglets (P<0.05). Developmentally, dIVS, dPW and %FS fell over time in CARN− (P<0.03), but not CARN + piglets. During hypoxia, dIVS, dPW, %FS and LVEV fell, but recovered partially after reoxygenation. ATP correlated with recovery dIVS, dPW and %FS. Heart ASTC and ASFC correlated with dPW, %FS during hypoxia. FC and ASFC correlated with ATP. Conclusions: Carnitine deprivation, in this piglet model, impairs cardiac performance over time and during and after hypoxia, probably due to poor energy production. Supported by the Little John Foundation, LSU Dept. of Pediatrics/Research Institute, and Louisiana EPSCOR (Pfund).