Reus has scored 17 goals and created 11 more for the Bundesliga leaders this season, but is absent for the last 16, first leg against Spurs at Wembley with a thigh strain.

“Now he’s also going to be missing for the important game against Tottenham – that won’t make it any easier,” said former Germany captain Matthaeus, now a Sky pundit.

“The third-best team in the Premier League against the best in the Bundesliga – I see the chances as 50/50.

“In Marco Reus, Dortmund are missing their best player.”

However, it is not just Reus who will be missing against Spurs.

Right-back Lukasz Piszczek is out with a heel injury, stand-in centre-back Julian Weigl has flu and striker Paco Alcacer is sidelined by a shoulder injury.

Reus injured his thigh last Tuesday while drilling home a direct free-kick against Werder Bremen, but Dortmund lost on penalties as the German Cup tie finished 3-3 after extra time.

Spurs are also without big names of their own as England forwards Harry Kane and Delle Alli are injured.

Matthaeus says Dortmund’s 3-3 draw at home to Hoffenheim on Saturday showed how much they miss Reus’ influence and organisation.

In his absence, Jadon Sancho, 18, already a full England international, has taken over playmaking duties and was outstanding in scoring a goal, setting up two more and hitting the post against Hoffenheim before Dortmund leaked three late goals.

“He (Reus) is the one who instils respect until the very end and has a controlling hand on the whole Dortmund game,” added Matthaeus.

“They have also won games without him and were 3-0 ahead on Saturday.”

Matthaeus says Saturday’s draw will have given hope to defending champions Bayern Munich, who closed the gap in the Bundesliga table to five points behind Dortmund with a 3-1 home win against Schalke on Saturday.

“The points Dortmund lost will have given Bayern a push, they’d have been inspired.”