The 15-time champions bested Brazil on penalties to reach the last four following a 0-0 draw in 120 minutes, but their success came at a major cost; both Ronald Araujo and Nahitan Nandez are now unavailable.
Araujo went off in the first half with a serious-looking leg injury, and the Barcelona centre-back is reportedly facing up to eight weeks out; a devastating blow for both club and country.
Meanwhile, Nandez was given a straight red card in the 74th minute for a dreadful challenge on Real Madrid winger Rodrygo, catching the Brazilian on his ankle with the full force of his studs.
With Nandez banned, Marcelo Bielsa has just one recognised right-back available in the shape of Guillermo Varela, and the former Manchester United man should therefore be a like-for-like swap.
Atletico Madrid star Jose Gimenez is the favourite to step in for Araujo, despite being the only Uruguay player to miss a penalty in the shootout, where Sergio Rochet denied Brazil centre-back Eder Militao.
Matias Vina and Mathias Olivera will complete a rejigged backline, but there will be no changes to the engine room, where Federico Valverde and Manuel Ugarte start behind Nicolas de la Cruz.
Despite his distressing fall in the 1-0 win over the USA, Maximiliano Araujo miraculously recovered in time to play the full 120 in the quarter-final, and the 24-year-old joins Facundo Pellistri and Darwin Nunez in another Luis Suarez-less attack.
Uruguay possible starting lineup:
Rochet; Varela, Gimenez, Olivera, Vina; Valverde, Ugarte; Pellistri, De la Cruz, Araujo; Nunez