The Qinghai–Tibet Plateau of China is a region of low atmospheric pressure and oxygen deficiency, with a high heating demand in the winter; therefore, plateau hotel buildings have a demand for comprehensive power-heating-oxygen loads. Solar energy resources are particularly abundant in plateau areas, where a combined multi-energy system based on solar energy can be designed to meet the demand of plateau hotel buildings for multiple loads. However, currently, there is a relative lack of methods for the optimal design and performance evaluation of combined power-heating-oxygen (CPHO) systems. Thus, this study proposes a CPHO system model for plateau hotels, and provides two operation strategies, i.e., power priority and oxygen priority. Taking the minimum total annual cost of the combined system as the optimization objective, an optimized CPHO system model for plateau hotels has been proposed, followed by a case study of a hotel in Qilian County, Qinghai Province. Results showed that: 1) Compared with the conventional combined power-heating (CCPH) system, the CPHO system saw reductions of 0.8% and 1.3% in its total annual cost under the operation strategies of power priority and oxygen priority, respectively. 2) The energy self-consumption (SC) rates of the CCPH system and CPHO system under the operation strategies of power priority and oxygen priority were 84.8%, 64.2%, and 89.8%, respectively; with power self-sufficiency (PSS) rates of 8.3%, 49.9%, and 29.5%, and oxygen self-sufficiency (OSS) rates of 0.0%, 3.2%, and 4.7%, respectively. 3) The total annual cost of the CPHO system was affected slightly by the cost of photovoltaics (PVs) and energy storage devices, and significantly by the price of oxygen. When the price of oxygen was 8 yuan per normal cubic meter(Nm3) or above, the CPHO system was economically efficient under the operation strategy of oxygen priority. When the price of oxygen was 10yuan/Nm3 or above, the system was economically efficient under both operation strategies.