This work is motivated by the need in overcoming the electricity crisis in Gaza, which is initiated due to political reasons and the spread of COVID‐19. Building quarantine centers is one of the most important means used in combating the COVID‐19, but connecting these centers to the electricity distribution network at the appropriate time is not always possible and increases the burden on the local utility company. This article proposed a hybrid off‐grid energy system (HES) to effectively energize the quarantine COVID‐19 center in Gaza economically and environmentally. To achieve this aim, the estimated load profile of the quarantine center is fed to the HOMER‐Pro program. In addition, the various systems components are introduced to the program, then modeled, and optimized. The developed approach was tested using a real case study considering realistic input data. HOMER‐Pro program is used to simulate and optimize the system design. The results revealed the potential of the HES to provide environment‐friendly, cost‐effective, and affordable electricity for the studied quarantine center, as compared to just the diesel generators system. For the considered case study, it is found that the PV‐wind‐diesel generators HES can cover the connected load with the lowest cost ($ 0.348/kWh) in comparison to other possible HES structures. Taking into consideration the price of harmful emissions, the wining system shows a reduction of 54.89% of the cost of energy (CoE) compared to other systems. For the considered case study, it is found that a combination of 150 kW PV, 200 kW wind, and two diesel generators with capacities of 500 and 250 kW can hold 100% of the electrical load required to keep the quarantine COVID‐19 center in operation. The initial capital cost of this HES is $510,576 where the share of wind energy, solar PV, inverter, and diesel‐electric generators are $320,000, $83,076, $25,000, and $82,500, respectively. The replacemen cost ($55,918) is due to diesel generators. The total operation and maintainance cost (O&M) is $268,737, that is, 25.6% for wind turbines, 1.2% for inverters, and 70.7% for diesel electric generators. The PV/wind/diesel generators HES generate 1,659,038 kWh of electricity. The total energy requirement of 1,442,553 kWh, which means a surplus of 212,553 kWh of energy/year. The total energy (kWh) is an integration of energy sources which are 427,276 (25.8%), 274,500 (16.5%), and 857,263 (57.7%), due to wind, solar and diesel generators respectively. The cost of yearly consumed fuel is $437,828.769. The payback period for the winning system is 1.8 years. Finally, it is proved that the developed approach gives a reasonable solution to the decision‐makers to find a fast, economic and reliable solution to energize the quarantine centers.