The pair have fallen short of expectations at Stamford Bridge since their arrival in deals worth a combined £120m over the summer.
Havertz has found the back of the net just five times in 32 outings, while Werner has managed a slightly more respectable haul of 10 goals in 39 games.
However, their struggles proved to be a major factor in the decision to dispense with Frank Lampard mid-season and replace him with Thomas Tuchel.
And, on the evidence of Wednesday evening, their poor form at club level could well be bleeding into the international stage.
Starting in an advanced position, Havertz failed to take a single shot before being withdrawn for Chelsea teammate Werner in the 56th minute.
Germany rallied after that change, with Ilkay Gundogan scoring from the penalty spot to cancel out Goran Pandev's opener.
However, with 10 minutes remaining, Werner missed a sitter from close range, badly scuffing his only shot of the match after good work from Serge Gnabry appeared to have set up a certain goal.
And North Macedonia made the most of the let-off, retaking the lead five minutes later through Eljif Elmas to claim a 2-1 victory.
That miss is unlikely to do Werner's confidence much good as he returns to Chelsea and refocuses on their bid for a top-four finish and Champions League hopes.
As for Havertz, he can take encouragement from having created two chances during his time on the pitch but, if suggestions his withdrawal was necessitated by a knock are indeed correct, then building on that boost could prove difficult.