Olivia Wilde has already had plenty of roles in her young career, but she’s known to most as the hipsterific lesbian who stole Marissa’s heart on The O.C., and for her more recent portrayal of stubbornly private second-generation intern Thirteen to Hugh Laurie’s good doctor House. The hit show’s fifth season kicks off tonight at eight and welcomes viewers back into the world of Princeton Plainborough Hospital, with the misanthropic doctor’s right-hand man Wilson (Robert Sean Leonard) threatening to jump ship and Thirteen is grappling with a diagnosis of Huntington’s chorea. Wilde spoke with Vulture about the upcoming season, her work for the Obama campaign, and Thirteen’s diagnosis with Huntington’s.

We read that you and Kal Penn campaigned for Obama and were involved in primaries. How did people react to you guys?
Well, what was really fascinating was that when we went to Iowa to caucus, we were welcomed with open arms, as House actors — House is apparently really big in Iowa, which was kind of a shock to me. We were in the middle of nowhere, and these House fans were, you know, chasing us around Wal-mart. But they also welcomed us as Obama supporters because there was a lot of enthusiasm there, particularly among the young people. They were literally out there pamphleting in ice storms and really working hard for him in a place where you would assumed they might not.

Sounds inspiring.
I totally caught the campaigning bug. I could have stayed on forever. And Kal really did. He has spent every minute he’s not shooting House back on the campaign doing anything he can.

So, House. What’s in store for Thirteen this season?
This season has been so incredible for Thirteen so far, and we’re only on episode ten! Mostly it’s her dealing with the tragic Huntington’s chorea diagnosis that she received at the end of season four. She knows it’s bad, and that causes her to lose control in a way that we didn’t expect from a character like her. She loves working for House because he’s the most brilliant person to work for, but she doesn’t want to fall into his traps. And so this tragic diagnosis causes her to lose control of all that, and now as she struggles to maintain the separation between her work life and her personal life; things sort of start to fall apart. As she scrambles to put them back together, she ends up making personal connections where you least expect them. And that makes for good television.

Thirteen just came out as bisexual, and your character on The O.C. was bisexual as well. Do you think it’s a vibe you’re giving off?
[Laughs.] This is only my second time playing a character who’s bisexual, and I’ve played a lot of straight people, but of course people don’t care about that. But in both of these cases the sexuality of the character was created before I met the writers. And I think in both cases, in The O.C. and in House, it’s not a situation where it’s two girls making out as a rating booster. It’s not some kind of Girls Gone Wild ploy. On House I definitely think it’s a great twist. Because whenever anyone sees a young woman in the same room with House, they think they’re going to get it on. And now, they’ve created this person who you don’t know, you know? If she’s in the same room with Cuddy, are you going to assume the same thing about them? I sort of love that it’s going to keep people guessing. You’re never going to be able to say, “Okay, yawn, now I know who’s going to get together. This is so predictable.”

Thirteen and Cuddy!
Yeah! You never know. I love Lisa. It’d be great.

Are you more of a hypochondriac now that you’ve filmed a whole season of House?

Well, it’s funny, because I was in Thailand in December and I got Dengue fever. It was awful, because for a while I had no idea what it was. And I kept thinking, If only I had House here with me!

Do you think anyone on the show will ever actually be diagnosed with lupus?
[Laughs.] I wonder. Have we ever actually had it be lupus? I feel like there may have been one person who, like, actually had Lupus. I can’t remember who it was. I mean, that’s a great example of people suddenly becoming aware of something from the show. I actually heard that the Lupus Foundation loves the fact that House has made it this famous phrase — “Is it lupus?’ It’s never lupus!” A lot of people had never heard of lupus before. It’s a good thing.

Definitely. So, the question of the day: Is Wilson really leaving Princeton Plainsboro!?
I think it’s a great risk that they’ve taken, taking this solid pillar of the show and shaken it up, weakened it to the point of collapsing. It’s not a permanent thing, this tragic separation between House and Wilson, but it’s not something that can be easily repaired. It takes a long time, and there are a lot of failed attempts at a quick patch-up. So that’s what I think is going to make people happy, to sort of see a lot more of Robert Sean Leonard, who is so incredible, obviously. He’s not gone forever — obviously I’ve given that away. But at first, they definitely have taken that risk and broken them apart. Broken up the romance. The bromance, as I’ve heard it called. Which is so funny.

‘House’ Star Olivia Wilde on Which Characters Thirteen Might Make Out With