Lee, Dustin Fletcher, Stewart Crameri, Angus Monfries and Michael Hibberd all come in to the team to take on North Melbourne in the highly anticipated clash at Etihad Stadium.
Jason Winderlich and Ben Howlett have been sidelined after the pair both suffered hamstring injuries last week, while Henry Slattery, Taye Pears and Cale Hooker have all been omitted from the side.
Fletcher, Crameri, Monfries and Hibberd are all returning from injury.
Lee was elevated to the club’s senior list this week, after veteran Mark McVeigh was placed on the long-term injury list with a knee injury.
The 24-year-old won East Perth's Best & Fairest and finished fourth in the Sandover Medal, racking up 500 possessions in the WAFL last year. The dashing midfielder boasts a big engine and wins a good mix of inside and outside ball.
With the inclusion of Lee, Essendon has had four debutants this year - including Elliott Kavangh, Mark Baguley and Cory Dell'Olio.