Uruguay have won only one out of their last six games against European opposition.
With 74 international appearances so far, Atletico Madrid's Diego Forlan is the most experienced Uruguay player in Wednesday's game.
Not a single teenager has been included in the South Americans' roster for the Oranje clash.
Uruguay last won a big trophy when they lifted the Copa America in 1995.
Ajax midfielder Nicolas Lodeiro is the only player in the Uruguay squad who currently plies his trade in the Dutch Eredivisie.
Netherlands have not lost a single match since their 1-0 loss against Spain in the final of the 2010 World Cup.
At the age of 31, Hamburg's Joris Mathijsen is the oldest player in the squad for this week's friendly.
Feyenoord youngster Georginio Wijnaldum is one of three Dutch players who could make his international debut on Wednesday.
Netherlands have met Uruguay five times before and were beaten on three occasions. Their only wins came in 2010 and 1974.
Schalke hitman Klaas-Jan Huntelaar sits ninth in the list of all-time Oranje goalscorers with 26 goals.
PROBABLE LINE-UPS
Uruguay (4-3-1-2)
Muslera; Caceres, Lugano, Godin, M. Pereira; Gargano, Perez, A. Pereira; Forlan; Cavani, Suarez
Head coach Oscar Tabarez could field the same eleven players who featured in the 2-1 friendly loss against Germany last week as he does not have too many injury worries. Sevilla's Martin Caceres was plagued by problems in the last weeks of the domestic season, but appears to be ready in time for the rematch of last World Cup's semi-final.
Goalscorers from that day Diego Forlan and Maxi Pereira are both present in the squad, as they look to banish memories of the 3-2 reverse in front of their own fans.
Netherlands (4-2-3-1)
Krul; Van der Wiel, Bruma, Mathijsen, Pieters; De Jong, Strootman; Robben, Afellay, Elia; Huntelaar
Netherlands tactician Bert van Marwijk will be without several regulars on Oranje's South America trip as Rafael van der Vaart, Wesley Sneijder, Mark van Bommel, Demy de Zeeuw, Theo Janssen, Michel Vorm and Maarten Stekelenburg have all stayed behind in Holland.
Shot-stopper Tim Krul made his debut against Brazil at the weekend and the Newcastle man is likely to start again. Nevertheless, Van Marwijk could make some changes compared to the team that locked horns with Brazil and Jeffrey Bruma, Eljero Elia and Klaas-Jan Huntelaar could all start on Wednesday.
Prediction
Uruguay will be keen to get a good result against Netherlands after their World Cup semi-final loss last year, but it will not be easy for the Charruas. They start the match as favourites as they are in full preparation for the Copa America, whereas Oranje's season is already over. Their recent record against European opposition is far from impressive though, while the Dutch have not lost a single game since their defeat against Spain in July 2010.
Uruguay 1-1 Netherlands 
