Orient dominated for long spells but Chesterfield, who were beaten 5-1 at Swansea a week earlier, defended doggedly and a goalless draw was just about right.
Clear cut chances were at a premium, but Orient skipper Gary Alexander should have put the home side in front after just four minutes.
He sprung the Chesterfield off-side trap when Shane Tudor floated in a free kick - but Orient's top scorer sent a tame header straight at visiting keeper Barry Roche.
After a slow start Orient started to exert some pressure but failed to find a way past the imposing Chesterfield defensive pairing of Steve Blatherwick and Reuben Hazell.
Indeed, although O's managed to keep their fourth successive clean sheet, the visitors locked dangerous on the break and Chesterfield almost stole the lead on 25 minutes when veteran Wayne Allison's 14-yard drive was bravely headed away by John Mackie.
Mackie then put his aerial ability to good use at the other end and watched an effort thud against the bar and post following Justin Miller's cross - but the O's defender was ruled marginally off-side.
Orient spurned another good chance on the stroke of half time when Matthew Lockwood and Tudor combined but Alexander fired the cross wide.
After the break Orient continued to press and Lockwood's superb cross field pass set up Tudor who lobbed agonizingly wide.
Chesterfield were restricted to long range efforts as Gareth Davies and then two snapshots from the impressive Derek Niven tested O's keeper Glyn Garner.
But Orient should have wrapped things up when Mackie's close range header was pushed away by keeper Roche and Gaby Zakauni's follow-up effort hit the post.
Zakauni then headed over before Orient sub Wayne Carlisle almost won the tie in the final minute with a shot that curled inches wide.