The Amsterdam giants travel to Twente, who pipped them to glory in 2009-10, while the Eindhoven heavyweights host AZ.
Since a 3-0 loss to Ajax in March, Twente have gone 16 matches unbeaten in all competitions. However, five draws from eight games ensures they only sit fifth in the Eredivisie, two points behind this weekend's opponents.
Ajax have not last in nine league meetings with Twente, who will charge Luc Castaignos with arresting that sequence. The 22-year-old former Inter striker has netted six times in his last five appearances in all competitions, to reportedly attract interest from abroad.
Frank de Boer will hope powerful striker Kolbeinn Sigthorsson, who helped Iceland beat the Netherlands in Euro 2016 qualifying, and 21-year-old playmaker Davy Klaassen can return Ajax to winning ways following back-to-back draws against APOEL and PEC Zwolle.
Phillip Cocu will bank on Luciano Narsingh maintaining his electrifying form against AZ, who have won two of their past three encounters with PSV.
Sixth host fourth in the Friesland derby, with the spotlight firmly on Dwight Lodeweges.
The Canada-born coach controversially left Cambuur to assume the Heerenveen reins in the summer, and is now plotting to extend his former employers' run of just one win from 21 Eredivisie away matches.
Lodeweges' successor at the Cambuur controls, Henk de Jong, will be without the suspended Michiel Hemmen but in former PSG and Nigeria player Bartholomew Ogbeche, he has a striker at the top of his game.
Third-placed PEC will look to young midfielder Jesper Drost at lowly Go Ahead Eagles, while Willem II and Vitesse meet in a mid-table contest.
Heracles extinguished a run of seven straight losses with their first victory of the campaign with a 6-1 thrashing of NAC Breda last time out.
Young Dutch midfielder Joey Pelupessy and Thomas Bruns will hope to inspire Heracles to back-to-back successes at Feyenoord.
NAC, down to fourth-bottom, look to bounce back when they entertain an ADO Den Haag side one place beneath them, while second-bottom Dordrecht host Utrecht.
Finally, injury-stricken Groningen seek a ninth consecutive home league win against Excelsior, who have seized just two points from a possible 12
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