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The 20-year-old replaced Tammy Abraham at half-time with the Blues 1-0 down.
But the 76th minute came round and manager Thomas Tuchel decided to hook him off for Hakim Ziyech.
Hudson-Odoi looked confused and frustrated as he walked off the pitch, with Tuchel giving him words of encouragement.
Hakim Ziyech and Jorginho coming on for Hudson-Odoi and Kovacic. Hudson-Odoi who was brought on at halftime but is now replaced after 30 minutes. It's still 1-1.#SOUCHE pic.twitter.com/6ZmYGR8kN5
- Lloyd Dsouza (@Lloyd_Dsouza03) February 20, 2021
Hudson-Odoi has been used as a wing-back since Tuchel's arrival last month and he's flourished.
But it wasn't his afternoon and fans have reacted to the youngster being subbed himself.
Callum Hudson-Odoi is the first Chelsea player to be subbed on and subbed off in the same Premier League game this season.- Squawka Football (@Squawka) February 20, 2021
Interesting to know what the reason might be. pic.twitter.com/pqEDqMLsae
Tuchel subbing the sub by taking Hudson Odoi off. No messing about with this boss- Mark Goldbridge (@markgoldbridge) February 20, 2021
Hudson Odoi heat map vs Southampton// Generational talent skills and highlights:snowflake: pic.twitter.com/eSX44Rnv5x- Luis Santaniello (@LuisSantaniell5) February 20, 2021
Absolutely ruthless from Thomas Tuchel to sub off Callm Hudson-Odoi after having subbed him on at half time.- EiF (@EiFSoccer) February 20, 2021
A bit of an odd one from the Chelsea manager - CHO hasn't been great but definitely hasn't been bad enough to be subbed off like that
Hudson Odoi subbed off at 75 minutes after only coming on at half time... And Chelsea fans still try to put this guy in the same bracket as Saka. :sob:- GoonerTalk (@GoonerTaIk) February 20, 2021
Callum Hudson-Odoi vs Southampton - Highlights: pic.twitter.com/XojbdhzJ7W- FPL Marcin (@FPLMarcin) February 20, 2021
Southampton took the lead in the first half thanks to on-loan Liverpool man Takumi Minamino.
Nathan Redmond played the Japanese international through and he took it under control perfectly.
Minamino then shimmied his body to the right, ensuring Cesar Azpilicueta committed himself to a challenge.
The 26-year-old slotted past Edouard Mendy as cool as you like to give the home side a shock lead.
Mason Mount grabbed the equaliser from the penalty spot after being fouled by Danny Ings.
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