Oxygen uptake (VO₂) is an important parameter in sports medicine, health assessment and clinical treatment. At present, more and more wearable devices are used in daily life, clinical treatment and health care. The parameters obtained by wearables have great research potential and application prospect. In this paper, an instantaneous VO₂ estimation model based on XGBoost was proposed and verified by using data obtained from a medical-grade wearable device (Beijing SensEcho) at different posture and activity levels. Furthermore, physiological characteristics extracted from single-lead electrocardiogram, thoracic and abdominal respiration signal and tri-axial acceleration signal were studied to optimize the model. There were 29 healthy volunteers recruited for the study to collect data while stationary (lying, sitting, standing), walking, Bruce treadmill test and recuperating with SensEcho and the gas analyzer (Metalyzer 3B). The results show that the VO₂ values estimated by the proposed model are in good agreement with the true values measured by the gas analyzer (R² = 0.94 ± 0.03, n = 72,235), and the mean absolute error (MAE) is 1.83 ± 0.59 ml/kg/min. Compared with the estimation method using a separate heart rate as input, our method reduced MAE by 54.70%. At the same time, other factors affecting the performance of the model were studied, including the influence of different input signals, gender and movement intensity, which provided more enlightenment for the estimation of VO₂. The results show that the proposed model based on cardio-pulmonary physiological signals as inputs can effectively improve the accuracy of instantaneous VO₂ estimation in various scenarios of activities and was robust between different motion modes and state. The VO₂ estimation method proposed in this paper has the potential to be used in daily life covering the scenario of stationary, walking and maximal exercise.

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