Chief Justice John Roberts announced that the court's oldest justice, at 86 years old, was "indisposed due to an illness" but would be following the week's cases by reading briefs from home. It's the second time within the past year that she has missed arguments due to an illness.
Her absence last December marked the first time in her 26 years on the bench that she had missed an argument.
The court's leading liberal on the bench, Ms Ginsburg and liberal and moderate justices are outnumbered 5-4 by conservative justices after the president's appointments of Neil Gorsuch and Brett Kavanaugh to the nation's highest court.
Ms Ginsburg appeared in court on Tuesday to hear oral arguments over the president's attempt to end the Deferred Action for Childhood Arrivals programme, or DACA, which has allowed more than 80,000 young people to legally remain in the country after entering the country as children with their undocumented families.
The court's five conservative justices could rule in favour of the Trump administration and argue that the Department of Homeland Security was allowed to end the programme in 2017.
Her absence from Wednesday's proceedings means she'll miss a Wednesday conference to discuss yesterday's hearing, including the DACA case. During Tuesday's proceedings, Ms Ginsburg had argued to a White House attorney that ending the programme would probably be unconstitutional, pointing to a Homeland Security memo that is "infected by the idea" of its illegality and "leaves substantial doubt about its illegality".
The Supreme Court could hear a number of high-profile cases this term that could potentially hand the administration and Republicans a number of victories in controversial cases, from anti-immigration policy to anti-abortion measures and efforts to strengthen Second Amendment protections.
Not yet scheduled this term are hearings to determine whether Louisiana can require physicians who perform abortions to have admitting privileges at a local hospital.
A four-time cancer survivor, Ms Ginsburg has faced a number of medical issues within the last year.
In August, she announced a procedure for a localised malignant tumour in her pancreas.
Last December, she had two cancerous nodes removed from her left lung.
Those procedures follow a 1999 surgery to treat colon cancer and treatment in 2009 for the early stages of pancreatic cancer.