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Mitra was born in Paddington, London, England, the daughter of Nora and Antony Mitra, who is a cosmetic surgeon. She has an older and younger brother. Her father is of Indian descent while her mother is Irish. In 1984, when Mitra was eight, her parents divorced and she was sent to boarding school. Several years passed at two different all-girls schools, including Roedean, but Mitra claims she was eventually expelled from both of them. She has been quoted as saying: "I was kicked out [of Roedean] for taking a sixth-former's car and driving it down to the local boys' school. I was only 14. I left stuffing under my bed sheets but one of my friends told on me and the headmistress tracked me down. They put me in this room with bars on the windows to punish me. I was stuck in there for a whole week with just a rosary for comfort, having my dinner brought in on trays. The only time I got out was to say confession to the school priest. After that, they booted me out. Then at the next school the other girls used to blame me whenever they got caught for something, so all the parents wrote in and said they didn't want me at the school. I crammed my exams in London and did fine."

Perhaps her first exposure to American audiences came as Scott Wolf's illicit love interest on Party of Five. In 2000, Mitra had a small, non-speaking part as a victim of the title role villain in the film Hollow Man. She appeared in the final season of The Practice as Tara Wilson, and continued that role into its spin-off Boston Legal, but left not long into the second season. She also appeared as the live action model for Lara Croft, the lead character in Eidos Interactive's Tomb Raider video game series. Mitra was ranked #46 on the Maxim Hot 100 Women of 2001. In 2005, she had a recurring role of Kit McGraw during Season 3 of Nip/Tuck.

In 2008, Mitra starred in the lead role of the science fiction/action film Doomsday.

• Underworld 3: The Rise of the Lycans (2009) Sonja
• Doomsday (2008) Eden Sinclair
• Shooter (2007) Alourdes Galindo
• Skinwalkers (2007) Rachel
• The Number 23 (2007) Laura Tollins
• Highwaymen (2004) Molly Poole
• Passion of the Priest (2004)
• Spartacus (2004)
• Stuck on You (2003) Bus Shop Bombshell
• The Life of David Gale (2003) Berlin
• Ali G Indahouse (2002) Kate Hedges
• Sweet Home Alabama (2002) Tabatha Wadmore-Smith
• Croupier (2000) Girl with Joint
• Get Carter (2000) Geraldine
• Hollow Man (2000)
• Beowulf (1999) Kyra
• A Kid in Aladdin's Palace (1998) Scheherazade
• Monk Dawson (1997) Mollie Jolliff/ Prostitute
• Boy in the Box Barbara

Had plastic surgery on her breasts to increase their size.

Once presented the Pepsi Chart Show (British Channel 5 show) with Dr. Fox.

Raised as a Catholic.

Went to Roedean, an all-girls' school in Brighton, East Sussex, but was expelled from it, then from another boarding school. According to Rhona, "I was kicked out for taking a sixth-former's car and driving it down to the local boys' school. I was only 14. I left stuffing under my bedsheets but one of my friends told on me and the headmistress tracked me down. They put me in this room with bars on the windows to punish me. I was stuck in there for a whole week with just a rosary for comfort, having my dinner brought in on trays. The only time I got out was to say confession to the school priest. After that, they booted me out. Then at the next school the other girls used to blame me whenever they got caught for something, so all the parents wrote in and said they didn't want me at the school. I crammed my exams in London and did fine."

Father was Antony Mitra (half-Indian, half-English), and mother Nora was Irish: they divorced in 1984.

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