The Eindhoven giants arrived at the game fresh off the back of a fantastic week, in which Napoli (6-2) and title rivals Feyenoord (3-2) were beaten in statement wins from the reigning Eredivisie champions.
With Ricardo Pepi back in the starting lineup, it was last week's hat-trick hero Ismael Saibari who hit the ground running again in Eindhoven. The Moroccan midfielder scored an early brace with a firm header and a fierce finish at Matthijs Branderhorst's near post.
Romanian international Dennis Man got PSV a three-goal lead on the cusp of halftime with a beautiful individual effort, outplaying two opponents before also beating Branderhorst at his near post.
Czech Bayer Leverkusen loanee Matej Kovar had a nightmare minute halfway through the second half - a bad pass got Fortuna Sittard the ball on PSV's half, after which a botched save earned Justin Lonwijk a surprising goal.
After Fortuna strikers Kaj Sierhuis and Paul Gladon wasted a chance by standing in each other's way, a lightning-quick counter saw Ricardo Pepi score PSV's fourth of the evening with a classy lob.
Kaj Sierhuis scored a beautiful consolation goal for Fortuna Sittard, striking the ball in the top corner from about 30 metres. PSV's Guus Til then ended the game once and for all, volleying in a Joey Veerman cross deep in extra time to win PSV the game 5-2.
PSV won their fifth game in a row across all competitions and played a perfect warm-up game ahead of Tuesday's UEFA Champions League meeting with Olympiakos.