Head coach Joe Schmidt has made five changes in personnel - three in the backs and two up front - as the province look to build on last weekend's 30-5 victory over Benetton Treviso.
Cullen joins fellow Ireland internationals Kevin McLaughlin, Rhys Ruddock and Devin Toner in the pack, with Stan Wright set for his second start of the campaign.
Bank of Ireland Player of the Month Isa Nacewa continues at full-back in a back-three which also includes recent try scorers David Kearney and Niall Morris.
McFadden links up with Eoin O'Malley at centre, and Sexton replaces his St. Mary's College club-mate Ian McKinley at out-half. He joins Isaac Boss at half-back.
Nathan Hines, who played for Scotland against Ireland last Sunday, is included amongst the replacements alongside Old Belvedere flyer Daniel Riordan, who previously played for Connacht and Munster.
Looking forward to the match, Kevin McLaughlin said: "We always like to think we're favourites at home. We pride ourselves on making the RDS a bit of a fortress.
"But we have to be wary. We played the Scarlets at the RDS three or four seasons ago, and they absolutely spanked us. We're very conscious of what they can do.
"They've a good offloading game, they've a couple of strong runners in the centres and good ball carries in the back row.
"We need to be conscious of their threats and shut them down, and then work on getting our own attacking game right."
Over 14,600 tickets have now been sold for Friday's game. Tickets are on sale from www.leinsterrugby.ie, Spar (Donnybrook), the Leinster Rugby Store (Donnybrook), Champion Sports (Grafton Street) and all Ticketmaster outlets nationwide.
There will be the usual 'Family Day' activities and tickets will also be on sale at the ground on the night.
LEINSTER (v Scarlets): Isa Nacewa; Niall Morris, Eoin O'Malley, Fergus McFadden, David Kearney; Jonathan Sexton, Isaac Boss; Heinke van der Merwe, Richardt Strauss, Stan Wright, Leo Cullen (capt), Devin Toner, Kevin McLaughlin, Dominic Ryan, Rhys Ruddock.
Replacements: Jason Harris-Wright, Jack McGrath, Simon Shawe, Nathan Hines, Paul Ryan, Paul O'Donohoe, Ian Madigan, Daniel Riordan.