Democratic vice presidential nominee Kamala Harris said foreign interference and voter suppression could potentially cost her and Joe Biden the White House.
November's election will be the first US election in more than a century to be conducted during a pandemic, which is expected to lead to a surge in mail voting.
President Donald Trump has repeatedly railed against mail balloting, which he argues will lead to widespread voter fraud.
For the first time in decades, both parties will be able to closely scrutinise who casts ballots due to a recent court ruling that wiped out tighter restrictions on poll monitoring.
US intelligence agencies have also concluded Russia is attempting to interfere in the election by amplifying discord in the country.
"I am a realist about it. Joe is a realist about it," Ms Harris said during an interview with CNN’s State Of The Union.
"We have classic voter suppression, we have what happened in 2016, which is foreign interference.
"We have a president who is trying to convince the American people not to believe in the integrity of our election system and compromise their belief that their vote might actually count.
"These things are all at play."
When asked directly if foreign interference could cost her and Mr Biden, the Democratic presidential nominee, the White House, she said: "Theoretically, of course, yes."
“I do believe that there will be foreign interference in the 2020 election and that Russia will be at the front of the line," she said.
Ms Harris also singled out a 2013 Supreme Court ruling which invalidated parts of the Voting Rights Act.
She said that has led some states to pass laws that are intended to limit access to the ballot for racial minorities.
Ms Harris said if she and Mr Biden win, they will make it a priority to try to restore those provisions.
"There will be many obstacles that people are intentionally placing in front of Americans’ ability to vote," she said.
Another issue Ms Harris touched on was Mr Trump’s handling of coronavirus and whether she would trust a vaccine that the president hopes will soon be available, even though medical experts have cautioned that more testing is needed.
"I would not trust his word," Ms Harris said.
"I would trust the word of public health experts and scientists, but not Donald Trump.