"When the exact same problems crop up in separate campaigns, with different staff, at what point do the principals say, 'Hey, maybe it's US?'" Axelrod tweeted, referencing the internal turmoil that gripped Clinton's losing 2008 bid.
Axelrod currently serves as a CNN senior political commentator.
Over the past several days, as the former secretary of state sought to make up ground in New Hampshire -- where she trails Bernie Sanders
by double-digits -- multiple reports have surfaced suggesting key members of her 2016 team were in danger of losing their jobs.
Top campaign pollster Joel Benenson, Axelrod's former colleague on the Obama team, is among the senior staff whose positions could be in jeopardy.
Appearing later on CNN's "AC360," Axelrod said Clinton's struggles had a "Groundhog Day-quality" to them, telling Anderson Cooper that remarks from President Bill Clinton in the last few days were to reminiscent of Hillary Clinton's last failed bid.
"Look at this weekend: Bill Clinton lashing out in a kind of a harsh way at Bernie Sanders last night, stories the day before the primary about a shakeup in the campaign. I don't see how this helps," Axelrod said.
Axelrod, who now hosts a podcast called "The Axe Files," tweeted
a link to his interview of Benenson just four hours before delivering his jab at the Clinton campaign "principals."
By late Monday afternoon, Clinton campaign chairman John Podesta moved to put out the fire, saying in his own tweet, "There is zero truth to what you may be reading. It's wrong. Hillary stands behind her team, period."
Clinton in 2008 replaced her campaign manager, Patti Solis Doyle, in early February. In April of that year, top pollster and longtime aide to her and former President Bill Clinton, Mark Penn, stepped down from his job amid infighting and questions over potentially conflicting private contracts.
Nevertheless, Axelrod said that Clinton's team should not overreact to her early challenges in Iowa and New Hampshire, stressing that later states on the map would wash away any concerns.
"If I were around her, I would say: 'Everybody chill, man'," he said.