The curtain raiser to the new campaign sees the O's travel to Sutton United, who famously caused a stir in the FA Cup last season.
Their manager Paul Doswell believes the division is so tough now and that Orient and fellow newcomers Hartlepool United are about to find out that there are some very strong teams outside the Football League.
Doswell commented: "It's an absolutely smashing first game and we're delighted with it. I actually wanted a game like this first of all.
"There is such an excitement about a big club coming to Sutton. We had a few of those here last year!
"The Vanarama National League is such an unforgiving division and every year the standard gets better and better and better.
"Both Orient and Hartlepool will find out all about that, there are so good sides down here and they are clubs that could equip themselves very well in League Two."
He added: "We can't wait, it's going to be another great occasion.
"The club will be showcased again like it was so much last year and we want to give another great Sutton performance and show people what we're made of."
The game is live of BT Sport, kick off at Gander Green Lane is 12.30pm.