The Moroccan giants do battle against the White Knight, who are still yet secure maximum points in Group D after back-to-back draws.
Wydad have only picked up one win so far, but a another win coupled with a Petro de Luanda loss against Sagrada Esperança will see the side move top.
Regragui insists that anything less than maximum points will be a disappointment on the night.
"Facing Zamalek is like a final for us. We must make sure to avoid any results that can affect our qualification," he told El-Botola.
Wydad come into the clash on the back of a loss in the Botola Pro this week, but the coach feels it may serve as a good motivator.
"We benefited from the defeat against Hassania Agadir before facing Zamalek," he concluded.
28. Kaizer Chiefs (South Africa)
18. Orlando Pirates (South Africa)
10. Wydad AC (Morocco)
9. CS Sfaxien (Tunisa)
8. Al Hilal (Sudan)
7. Etoile du Sahel (Tunisia)
6. Al-Merreikh (Sudan)
4. Zamalek (Egypt)
3. TP Mazembe (DR Congo)
2. Esperance (Tunisia)
1. Al Ahly (Egypt)
5. Mamelodi Sundowns (South Africa)