Simek missed the Birmingham friendly due to precautionary reasons but is now fully fit after recovering from a knock.
It is expected that he will line up in a defence with Lee Bullen, Richard Wood and Peter Gilbert - who will protect debutant goalkeeper Lee Grant.
Jermaine Johnson should take the right-wing berth although Wade Small has had a fantastic pre-season and could push the Jamaican all the way for a starting berth.
Glenn Whelan will be reunited with Steve Watson after their midfield partnership helped Wednesday finish last season on a high before the Geordie's return to West Brom.
Chris Brunt will start on the left before being forced to miss the following three games due to a sending off during the tour of Holland.
It is expected that Jeffers, signed yesterday from Blackburn Rovers, will start in attack with Marcus Tudgay with Deon Burton still feeling the effects of a knee injury suffered against Oldham.
New boys Richard Hinds and Robert Burch should be on the bench as The Owls head down to Suffolk for tomorrow's season opener.