Santos was appointed as Paulo Bento's replacement last month following Portugal's humiliating 1-0 loss to Albania in their Group I opener, although he is currently subject to an eight-game ban by FIFA for misconduct during Greece's World Cup last-16 penalty shootout loss to Costa Rica.
That ban, upheld on appeal by FIFA, will see him unable to oversee things from the touchline in Saturday's friendly with France or the clash with Denmark - who Portugal have not beaten away from home since 1995.
Albania host Denmark three days earlier hoping to inflict a similar shock on the Scandinavians before visiting a Serbia side that will be coming off a challenging away game in Armenia.
World champions Germany travel to neighbours Poland before welcoming the Republic of Ireland to the Veltins-Arena in Gelsenkirchen next Tuesday.
And coach Joachim Low is keen for his side to take command of Group D with victories in both encounters.
"Both of these games in October are extremely important," he told the German Football Association's website.
"If we are successful against Poland and then afterwards against Ireland, then we could give ourselves a cushion."
Ireland's clash with Germany comes after a meeting with international newboys Gibraltar, who then host Georgia.
Scotland, who lost 2-1 to Germany in their opening fixture, entertain Georgia and then visit Poland as they aim to build on an encouraging performance in Dortmund last time out.
Reigning European champions Spain will be expected to claim maximum points from away games with Slovakia and Luxembourg, who also meet Belarus and Macedonia respectively, in Group C.
Ukraine, beaten 1-0 by Slovakia in their opener, are arguably favourites for second spot behind Spain and will be eager to recover versus Belarus and Macedonia.
Italy, defeated by Spain in the Euro 2012 final, should be expected to continue their good start under Antonio Conte against Azerbaijan and Malta, but Group H rivals Bulgaria face much tougher assignments versus Croatia and Norway.
Norway, beaten 2-0 by Italy in their opener, will also take on Malta while Croatia's other game is with Azerbaijan.
Netherlands suffered a surprise defeat in their opening fixture in Group A, losing 2-1 at Czech Republic, but should be confident of that setback by beating Kazakhstan and Iceland.
Trips to Turkey and Kazakhstan beckon for the Czech Republic as they seek to gain some comfort room at the top of the group and Latvia will welcome Iceland and Turkey to Riga.
Group B sees World Cup quarter-finalists Belgium open their campaign against Andorra and Bosnia-Herzegovina, while Israel travel to Cyprus and Andorra following the suspension of last month's meeting with Marc Wilmots' men due to safety fears.
Wales, meanwhile, host Bosnia-Herzegovina and Cyprus after narrowly avoiding an embarrassing result in their 2-1 victory over Andorra.
England made a fine start to their Group E campaign with a 2-0 win at Switzerland and are likely to have little difficulty overcoming San Marino and Estonia this week, despite the absence of striker Daniel Sturridge.
Lithuania host Estonia and Slovenia, who will also be looking to inflict further pain on Vladimir Petkovic's Switzerland ahead of their trip to San Marino.
Greece, famous winners in 2004, meet Finland and Northern Ireland in Group F after coming unstuck in the opener against a Romania side that will attempt to build on their 1-0 triumph in Piraeus with wins over Hungary and Finland.
Pool minnows the Faroe Islands face Northern Ireland and Hungary in their search for a first competitive win since June 2011.
Elsewhere, Group G favourites Russia take on Sweden and Moldova, and Montenegro meet Liechtenstein and Austria.
The group's other games see Austria visit Moldova and Sweden host Liechtenstein.
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