Mauricio Pochettino told reporters on Tuesday that James would be making his first start since the opening day of the season after coming through two substitute outings since the international break.
Meanwhile, Fernandez was a surprise absentee from the Brentford fixture on Saturday with a muscle injury, but he is deemed fit enough to feature at Stamford Bridge.
Benoit Badiashile also comes in for his first start of the season after recovering from a hamstring injury, while Lesley Ugochukwu is the fourth and final alteration to the team.
Thiago Silva does not feature in the squad, while Levi Colwill, Moises Caicedo and Noni Madueke have all dropped down to the substitutes' bench.
Despite drawing a blank against the Bees, Cole Palmer, Raheem Sterling and Nicolas Jackson are selected as the front three.
Meanwhile, Blackburn boss Jon Dahl Tomasson has made six changes to the side that started the 1-0 defeat at home to Swansea City.
Lewis Travis, Adam Wharton, Jake Garrett, Dilan Markanday, Andrew Moran and Harry Leonard have all been drafted into the first XI.
Chelsea: Sanchez; James, Disasi, Badiashile, Cucurella; Ugochukwu, Fernandez, Gallagher; Palmer, Jackson, Sterling
Subs: Petrovic, Colwill, Gusto, Maatsen, Caicedo, Madueke, Matos, Castledine, Deivid
Blackburn Rovers: Wahlstedt; Brittain, Carter, Hill, Pickering; A.Wharton, Travis, Garrett; Markanday, Leonard, Moran
Subs: Hilton, S.Wharton, Gamble, Batty, Rankin-Costello, Tronstad, Sigurdsson, Dolan, Ennis