Interracial marriage was illegal in Maryland before 1967, so in 1958 O'Brien's parents married in Washington, D.C., where marriage laws were less restrictive. The newly wedded O'Briens then moved to Long Island, to the town of St. James. O'Brien is the fifth of six children, all graduates of Harvard College. Her siblings are law professor Maria Hylton (born 1960), GE corporate lawyer Cecilia Vega (born 1961), businessman Tony O'Brien (born 1962), who heads a documents company, eye surgeon Estela Ogiste (born 1964), and anesthesiologist Orestes O'Brien (born 1967).