Prolonged use of tight-fitting PPE, e.g., by COVID-19 healthcare workers leads to skin injuries. An important contributor is the shear exerted on the skin due to static friction at the skin-PPE interface. This study aims to develop an optimised wax-oil lubricant that reduces the friction, or shear, in the skin-PPE contact for up to four hours. Lubricants with different wax-oil combinations were prepared using beeswax, paraffin wax, olive oil, and mineral oil. In-vivo friction measurements involving seven participants were conducted by sliding a polydimethylsiloxane ball against the volar forearms to simulate the skin-PPE interface. The maximum static coefficient of friction was measured immediately and four hours after lubricant application. It was found that the coefficient of friction of wax-oil lubricants is mainly governed by the ratio of wax to oil and the thermal stability and morphology of the wax. To maintain long-term lubricity, it is crucial to consider the absorption of oil into the PPE material. The best performing lubricant is a mixture of 20 wt% beeswax, 40 wt% olive oil, and 40 wt% mineral oil, which compared to unlubricated skin, provides 87% (P = 0.0006) and 59% (P = 0.0015) reduction in instantaneous and 4-h coefficient of friction, respectively.