A rep for the singer has confirmed the news to Us Weekly, with reports from Lopilato's native Argentina suggesting that she is approximately 2.5 months along in her pregnancy.
The happy family news comes after the couple's four-year-old son Noah's heartbreaking battle with cancer.
Their eldest son was diagnosed with liver cancer in November 2016, and underwent treatment last year.
In December 2017, it was reported that Noah was doing much better.
Bublé, 42, and Lopilato, 30, are also parents to Elias, 2.