Gary Cahill returns to the starting line-up with Branislav Ivanovic on the bench.
With David Luiz remaining in defence, Frank Lampard continues alongside Ramires in midfield. Oscar replaces Ryan Bertrand with Demba Ba selected as centre-forward.
John Terry is again among the subs.
Compared with the cup game 11 days ago, Southampton right-back Nathaniel Clyne returns with Jack Cork moving to midfield and James Ward-Prowse making way. Jos Hooiveld replaces injured captain Jose Fonte. Jay Rodriguez is again preferred to Rickie Lambert in attack.
Chelsea are expected to line up in the following 4-2-3-1 formation:
1 Petr Cech
28 Cesar Azpilicueta
24 Gary Cahill
4 David Luiz
3 Ashley Cole
8 Frank Lampard (c)
10 Juan Mata
17 Eden Hazard
29 Demba Ba
Substitutes: 22 Ross Turnbull, 2 Branislav Ivanovic, 19 Paulo Ferreira, 26 John Terry, 34 Ryan Bertrand, 21 Marko Marin, 9 Fernando Torres.
Southampton are expected to line up in the following 4-2-3-1 formation:
Boruc; Clyne, Hooiveld, Yoshida, Shaw; Schneiderlin (c), Cork; Puncheon, S Davis, Do Prado; Rodriguez.
Substitutues: K Davis, Fox, Ward-Prowse, Ramirez, Seaborne, Chaplow, Lambert.
The referee is Michael Oliver.
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