'Strange Love' will appear over the end credits of the film and also be included on the 14-track Frankenweenie Unleashed! compilation.
"Tim wanted an unconventional unconditional-love song," Karen O told Rolling Stone.
"My music inspiration came out of the same era of B movie fright film references sprinkled throughout the film."
She added: "I went in the direction of exotica and calypso stylistically because it's quirky, good vibes music of that era and when you throw in a theremin solo it's a marriage made in heaven.
"I remember Beetlejuice introducing me to the genius of Harry Belafonte's calypso record so I wanted to give a nod to that too.
"We ended up with a love song for the end of the film to the film! Frankenweenie is so special, it's an unbelievable honour to be involved with it."
The full Frankenweenie Unleashed! tracklisting is follows:
1. 'Strange Love' - Karen O
2. 'Electric Heart (Stay Forever)' - Neon Trees
3. 'Polartropic (You Don't Understand Me)' - Mark Foster
4. 'Almost There' - Passion Pit
5. 'Pet Sematary' - Plain White T's
6. 'With My Hands' - Kimbra
7. 'Everybody's Got a Secret' - AWOLNATION
8. 'Immortal' - Kerli
9. 'My Mechanical Friend' - Grace Potter featuring The Flaming Lips
10. 'Lost Cause' - Imagine Dragons
11. 'Underground' - Grouplove
12. 'Building a Monster' - Skylar Grey
13. 'Witchcraft' - Robert Smith
14. 'Praise Be New Holland' - Winona Ryder
The Yeah Yeah Yeahs frontwoman previously co-wrote the score for 2009 film Where the Wild Things Are and co-wrote the Grammy and Golden Globe-nominated song 'All Is Love' with her bandmate Nick Zinner.
Frankenweenie Unleashed! will be released on September 25 and October 15 in the UK. The Frankenweenie original motion picture soundtrack with score by Danny Elfman will also be available on September 25.
Frankenweenie is released in US cinemas on October 5 and October 17 in the UK.
Watch the Frankenweenie trailer below: