Hemorrhagic hypovolemia and inotropic agent administration were used to manipulate cardiac output (CO) and oxygen delivery in rabbits to investigate the correlation between noninvasive frequency domain photon migration (FDPM) spectroscopy and invasive hemodynamic monitoring parameters. Frequency-domain photon migration provides quantitative measurements of light absorption and reduced scattering (µa and µ's, respectively) in tissue. Wavelength dependent µa values were used to calculate in vivo tissue concentration of deoxyhemoglobin [Hb], oxyhemoglobin [HbO2], total hemoglobin [TotHb], and water [H2O] as well as mixed arterial-venous oxygen saturation (StO2) in tissue. FDPM-derived physiologic properties were correlated with invasive measurements of CO and mean pulmonary artery pressure (mPAP), FDPM-derived [TotHb] and StO2 correlated significantly with hemorrhaged volume (HV), mPAP, and CO. Correlation coefficients for [TotHb] vs HV, mPAP, and CO were ?0.77, 0.86, and 0.70, respectively. Correlation coefficients of StO2 vs HV, mPAP, and CO were ?0.71, 0.55, and 0.61, respectively. Dobutamine induced changes resulted in correlation coefficients between FDPM-derived and invasively measured physiologic parameters that are comparable to those induced by hypovolemia. FDPM spectroscopy is sensitive to changes in mPAP and CO of as little as 15%. These results suggest that FDPM spectroscopy may be used in clinical settings to noninvasively monitor central hemodynamic parameters and to directly assess oxygenation of tissues.