Crows captain Nathan van Berlo ruptured an Achilles tendon in a training accident, when a weights sled cannoned into him - whether he plays this year is doubtful.
And Sanderson's sage, his strategy and innovation coach Dean Bailey, has chest cancer - whether he beats it and returns to the coaching box is unknown.
Sanderson says the dual blows "have really knocked us around".
"They are two things that you would never, ever plan for," Sanderson told AAP.
"VB's injury was just a freak one that if you tried to replicate or simulate ever again, you never could.
"And unfortunately with Dean, our prayers are with him at the moment because he's going through a tough fight."
Sanderson took Adelaide to a 2012 preliminary final in his first year in charge, but it was followed by a hellish period entering last season.
The Kurt Tippett saga cost the Crows dearly: not only did Tippett quit the club, Adelaide's chief executive and football manager were suspended for the salary cap rort and Sanderson lost four choice draft picks.
Then, Bailey was banned for 16 games for his role, when Melbourne coach, in alleged tanking.
And when Sanderson's second season in charge got under way, he lost his game-breaker when key forward Taylor Walker wrecked a knee in round five and required a reconstruction.
Walker's absence led to Adelaide scoring, on average, almost three goals a game less than the previous year.
The Crows subsequently wobbled to 11th spot with 10 wins (just one against a finalist) and 12 losses (five by two goals or fewer).
"When we lost Tippett and then Walker got injured, we did have to change the way that we played," Sanderson said.
"The one thing that wasn't settled was our forward group, we had a lot of different names and faces go through there."
So Sanderson went shopping, and bolstered his attack with ex-Carlton goalsneak Eddie Betts and sticky-fingered James Podsiadly from Geelong.
Walker will return "certainly in the first third, if not the first quarter of the season", said Sanderson.
The coach admits uncertainty at how the forwards will jell with the likes of last year's leading goalkicker Tom Lynch, though has no such worries with a midfield he rates as top-notch.
Headed by Patrick Dangerfield and Rory Sloane, who will share the captaincy in van Berlo's absence, the on-ball brigade includes renowned ruck Sam Jacobs, battle-hardened club champions Scott Thompson and Richard Douglas, emerging star Brad Crouch, and a batch of youngsters like Sam Kerridge, Jarryd Lyons and Mitch Grigg itching for opportunity.
"I wouldn't swap our midfield for anyone ... they're worthy of being called A-grade," Sanderson said.
Adelaide's defence will again be underpinned by talls Ben Rutten and Daniel Talia, with unsung backmen Brodie Smith, Luke Brown and Rory Laird.
"I do like that group. There is no fanfare about them, they just get the job done," he said.
But there is an area of utmost concern for Sanderson: tackling. In his two seasons, the Crows have ranked 17th and 16th for tackles laid.
"It's one area that we have really focused on in the summer," he said.
"We have done a lot of tackling work in the sand pit, upstairs on the tackle mats, and then we have been doing drills on the track - but nothing can really compare to getting out and hitting bodies in games."
