The Cairo-based 'White Knights' launch their bid for a 1.5-million-dollar first prize and a place at the 2011 FIFA Club World Cup in Japan with a game against Kenyan military outfit Ulinzi Stars in Nairobi.
It is the second successive year that the first round draw delivered a fixture involving clubs from the countries, with 1969 champions Ismailia eliminating Sofapaka 2-0 on aggregate a year ago.
Zamalek have been crowned champions five times since 1984 – once less than record holders and Cairo neighbours Al-Ahly – with their last successful run coming nine years ago against Raja Casablanca of Morocco.
After being overshadowed domestically by Ahly for most of the last decade, Zamalek are enjoying life under coach Hossam Hassan and top the league table halfway through the season with Ahly six points adrift.
The Egyptians named temperamental midfielder Mahmoud 'Shikabala' Fadlallah in a 21-strong squad for the journey down east Africa to Kenya after he was initially axed following a verbal clash with club football director Ibrahim Hassan.
Former Wigan Athletic striker Amr Zaki, a star of Egypt's 2008 African Nations Cup-winning team, has been ruled out due to a knee injury while Ivorian Aboubakar Kone is among four strikers chosen.
Injuries have dealt a triple blow to Ulinzi, who clinched the title on the final day of the season, with captain and midfielder Stephen Ocholla, defender Tom Onyango and striker striker Kevin Simiyu absent.
Kenyan clubs invariably come off second best against Egyptian opposition in African competitions, but coach Benjamin Nyangweso believes Stars can buck the depressing trend.
"We cannot be cowed by Zamalek despite their pedigree and rich history in this competition. I know many of their players helped Egypt hammer Kenya 5-1 recently but we are ready for the challenge," he said.
Enyimba of Nigeria, Mouloudia Alger of Algeria, Club Africain of Tunisia and Vita Club of the Democratic Republic of Congo are other former champions who are away in the first leg.
Saint Michel Ouenze of Congo could be a 'banana skin' for off-form Enyimba and Mouloudia will not relish facing Real Bangui in the Central African Republic, where 2010 World Cup qualifiers Algeria were humbled last October.
Club Africain have made little impact since conquering Africa 20 years ago and must be wary of Rwandan military club APR while Vita should find the going easier against African debutants Ocean View on the island of Zanzibar.
Casablanca giants Raja and Wydad host Tourbillon of Chad and Aduana Stars of Ghana respectively with the latter facing the tougher task and ASEC Mimosas of Ivory Coast should prove too strong for Mauritanian visitors Cansando.
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