Spurs, who are nine points below the top four, exited the Europa League on Thursday night, despite giving Benfica a scare in Portugal during a 2-2 draw at the Estadio da Luz.
The North London club's season appears to have fizzled out, but Sherwood insists that his side, who have only scored 16 goals in 15 home league games this term, remain fully motivated.
"Anyone who watched the performance against Benfica will not want to play us," Sherwood told Tottenham's official club website. "We are very buoyant now. This has been a real positive.
"Southampton have good, young English players and a good playing system, but we want them to worry about us and we'll go for it.
"Between now and the end of the season, we're going to have a real go."
Spurs have won their last three matches against Southampton. The Saints' last victory at White Hart Lane was a 3-1 success in September 2003 - a result that was followed by the sacking of Glenn Hoddle.