In 1930, the Council of the Order proposed re-establishing an administrative link to the traditional protectors of the House of Borbón, and in December 1935, H.R.H. Francisco de Paula de Borbón y de la Torre, Duke of Seville and Grandee of Spain (a second cousin of King Alfonso XIII) was appointed the 44th Grand Master of the Order. The Duke worked towards the revitalization of the Order by rallying the knights to its traditional double mission: aid to lepers and collaboration in the defence of the Christian Faith. This administrative re-orientation led to the recognition of the Orden Hospitalaria de San Lazaro de Jerusalen by the Spanish Ministry of the Interior in 1940.
After the Second World War the Order's expansion reached its zenith. In 1948, the statutes of the Order were revised as a summation of all the previous Statutes and Decrees of the Order. Membership grew as did its charitable missions. The Duke of Seville moulded some of the Order's ancient traditions with modern reforms with evident success. The Order, wishing to revert to its original mission, became actively involved in the care of lepers in Spain and in 1946 General Franco associated the Order with the national fight against leprosy, skin disorders and sexual diseases.