Hummels was an unused substitute for Germany after losing his place for the qualifiers against Austria and the Faeroe Islands, while Subotic put his international career on hold after Serbia failed to secure qualification.
Hummels, in particular, is cause for concern.
Klopp substituted the defender in the side's previous league game because he was "in danger of a red card" and Hummels was heavily criticized for his performance in the Germany's 3-3 draw with Paraguay in a friendly last month.
"Footballers are only people," said Klopp, angrily rejecting the criticism on Thursday.
"Now you're making history of Mats Hummels because he didn't play in two international games," Klopp said. "He made a very good impression in training yesterday. ... I'm happy he's a Dortmund player, happy he will play many more years for Borussia Dortmund."
Germany coach Joachim Loew suggested the 24-year-old Hummels was merely going through a bad patch.
"In comparison to last year, he's lacking a little assurance," Loew said. "But I'm a huge fan of his. He's a great player and of course we'll continue to rely on him."
Sven Bender was another unused substitute for Germany, Nuri Sahin likewise for Turkey, but Dortmund players Marcel Schmelzer, Henrikh Mkhitaryan and Sokratis all played for their respective national sides.
Attacking midfielder Marco Reus is expected to face Hamburg after recovering from the stomach infection that caused him to miss Germany's 3-0 win in the Faeroe Islands, but Ilkay Gundogan remains out with back problems.
"It's definitely better, even if not yet perfect," Gundogan said. "Everything is getting back to normal but I still need a bit of patience.
Hamburg is hopeful Dutch star Rafael van der Vaart can play as the hamstring injury suffered on international duty turned out not to be as bad as initially feared.
"I feel fit at the moment," van der Vaart said after playing 30 minutes in a test game against Hamburg's under-23s on Wednesday.
Klopp said his side has "something to make good on" after losing both league games to Hamburg last season.
Bayern Munich hosts Hannover on Saturday, when the team aims to bounce back with a win after dropping points against Freiburg before the UEFA Super Cup win over Chelsea.
Mario Goetze, Thiago Alcantara and Javi Martinez have joined long-term absentee Holger Badstuber on the injury list, while Bayern is waiting to see if Bastian Schweinsteiger has recovered from the right ankle injury that ruled him out of Germany's qualifiers.
"Now it starts," said Bayern winger Arjen Robben, whose side begins the defense of its Champions League title at home to CSKA Moscow on Tuesday.
"We need all our players. So it's a pity that three important players are out already," Robben said.
Also Saturday, Bayer Leverkusen hosts Wolfsburg, Eintracht Frankfurt visits Werder Bremen, Mainz plays Schalke, and Augsburg hosts Freiburg, which is already struggling to deal with a host of summer departures following the modest club's remarkable success last season. Christian Streich's side is still looking for its first win.
Goals are expected when Hoffenheim hosts Borussia Moenchengladbach on Sunday. There have been 24 goals in the four games involving Hoffenheim so far, and 18 in the matches involving 'Gladbach.
Also Sunday, Eintracht Braunschweig is desperate for a good result against Nuremberg after four straight defeats on its return to the Bundesliga after 28 years.
Nuremberg has only two points to show from its games so far, however, and will target its first win in Braunschweig since Oct. 30, 1968.
Hertha Berlin hosts Stuttgart to get the fifth round of games under way on Friday.