- Younger sister of Seth MacFarlane. Their father, Ron MacFarlane, narrated the hour-long Christmas episode of Les Griffin (1999), Road to the North Pole (2010), and the hour-long season 9 premiere, And Then There Were Fewer (2010), was dedicated to their mother, Perry MacFarlane (Ann Perry Sager MacFarlane), who died of cancer in 2010.
- Distant cousin of Ashley Judd. Both are descendants of William Brewster and wife Mary, who came over to Massachusetts, America, on the Mayflower.
- She has been married to animator Spencer Laudiero since 2008. They have two daughters together: Bella Francesca Laudiero (born in November 2009) and Perrin Elizabeth Laudiero (born in June 2015).
- She has English, Scottish, and Irish ancestry.
- Once lived in Wrentham, Massachusetts.
- Cousin Tim Mercer has a punk-pop band in Brooklyn, New York.
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