We propose a method to perform simultaneous measurements of percutaneous arterial oxygen saturation (SpO 2), tissue oxygen saturation (StO 2), pulse rate (PR), and respiratory rate (RR) in real-time, using a digital red–green–blue (RGB) camera. Concentrations of oxygenated hemoglobin (C HbO), deoxygenated hemoglobin (C HbR), total hemoglobin (C HbT), and StO 2 were estimated from videos of the human face using a method based on a tissue-like light transport model of the skin. The photoplethysmogram (PPG) signals are extracted from the temporal fluctuations in C HbO, C HbR, and C HbT using a finite impulse response (FIR) filter (low and high cut-off frequencies of 0.7 and 3 Hz, respectively). The PR is calculated from the PPG signal for C HbT. The ratio of pulse wave amplitude for C HbO and that for C HbR are associated with the reference value of SpO 2 measured by a commercially available pulse oximeter, which provides an empirical formula to estimate SpO 2 from videos. The respiration-dependent oscillation in C HbT was extracted from another FIR filter (low and high cut-off frequencies of 0.05 and 0.5 Hz, respectively) and used to calculate the RR. In vivo experiments with human volunteers while varying the fraction of inspired oxygen were performed to evaluate the comparability of the proposed method with commercially available devices. The Bland–Altman analysis showed that the mean bias for PR, RR, SpO 2, and StO 2 were -1.4 (bpm), -1.2(rpm), 0.5 (%), and -3.0 (%), respectively. The precisions for PR, RR, Sp O 2, and StO 2 were ±3.1 (bpm), ±3.5 (rpm), ±4.3 (%), and ±4.8 (%), respectively. The resulting precision and RMSE for StO 2 were pretty close to the clinical accuracy requirement. The accuracy of the RR is considered a little less accurate than clinical requirements. This is the first demonstration of a low-cost RGB camera-based method for contactless simultaneous measurements of the heart rate, percutaneous arterial oxygen saturation, and tissue oxygen saturation in real-time.