Background: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. Objectives: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. Methods: 11 patients (GA 26.6-33.0 weeks, BW 780-2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4-33.3 weeks, BW 842-1,955 g) were sedated with morphine (loading dose 0.05 mg/kg, maintenance 0.01 mg/kg/h). Changes in oxyhemoglobin ($Δ$cO2Hb) and deoxyhemoglobin ($Δ$cHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= $Δ$cO2Hb - $Δ$cHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin ($Δ$ctHb = $Δ$cO2Hb + $Δ$cHHb) represent changes in cerebral blood volume ($Δ$CBV). Changes in cerebral blood flow velocity ($Δ$CBFV) were intermittently measured using Doppler ultrasound. Heart rate (HR), mean arterial blood pressure (MABP), arterial oxygen saturation (saO2) and transcutaneous measured pO 2 (tcpO2) and pCO2 (tcpCO2) were continuously registered. Statistical analyses were carried out using linear mixed models to account for the longitudinal character study design. Results: Within 15 min after the loading dose of midazolam, a decrease in saO 2, tcpO2 and cHbD was observed in 5/11 infants. In addition, a fall in MABP and CBFV was observed 15 min after midazolam administration. Immediately after morphine infusion a decrease in saO 2, tcpO2 and cHbD was observed in 6/10 infants. Furthermore, morphine infusion resulted in a persistent increase in CBV. Conclusions: Administration of midazolam and morphine in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful. Copyright © 2006 S. Karger AG.