Jamie Vardy scored a vital away goal for Leicester
Sevilla started the brighter of the two sides and looked set to take a 1-0 lead from the penalty spot when Joaquin Correa was fouled in the box by Wes Morgan.
Correa stepped up to take the spot-kick but never looked confident and his effort was easily saved by Kasper Schmeichel.
However, the home side soon made amends and took the lead after a quarter of an hour courtesy of Pablo Sarabia.
Joaquin Correa doubled Sevilla's lead in the second-half
Jamie Vardy gave the Leicester fans something to cheer
The 24-year-old climbed above Christian Fuchs at the back post to head home a powerful header following an inviting ball from Sergio Escudero.
Sevilla then doubled their advantage after the break as Correa made up for his earlier penalty miss.
The 22-year-old gathered a clever lay-off from Stefan Jovetic and fired into the roof of the net beyond the sliding Morgan.
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At 2-0 it looked like Leicester's European form had deserted them, much like their recent showings in the Premier League.
However, up stepped Jamie Vardy on 73 minutes to give the travelling Foxes fans something to cheer about.
The England international latched onto a smart ball from Danny Drinkwater and fired it past Sergio Rico emphatically in the Sevilla goal.
Despite the defeat, the away goal keeps the tie alive for Claudio Ranieri's men who will face Sevilla in the second leg on March 14.