As　working　for　the　nurse　is　believed　to　be　one　of　the　most　stressful　professions,　nurses　are　particularly　at　risk　of　experiencing　fatigue.　Especially　during　the　COVID-19　pandemic,　fatigue　among　nurses　may　affect　physical　and　mental　health　seriously,　which　is　attracting　increasing　attention　of　researchers　and　clinical　practitioners　to　find　effective　prevention　measures　to　alleviate　nurses＇　fatigue.　This　study　aims　to　investigate　the　mediational　effect　of　resilience　on　the　relationship　between　nurses＇　perceived　organizational　support　and　fatigue.　A　total　of　476　nurses　from　secondary　and　above　hospitals　in　Hebei　province,　China　during　March　and　April　in　2020,　were　investigated　with　Perceived　Organizational　Support　Scale,　Resilience　Scale　and　Work　Fatigue　Inventory.　Structural　equation　modeling　was　conducted　to　explore　the　mechanisms　of　nurses＇　perceived　organizational　support　on　fatigue.　Results　revealed　that　perceived　organizational　support　can　decrease　the　nurses＇　mental/physical/emotional　fatigue　through　the　mediating　role　of　resilience.　These　findings　guide　for　hospital　managers　to　identify　effective　prevention　strategies　to　alleviate　the　fatigue　of　clinical　nurses.