US experts found B3, also known as nicotinamide, boosts the ability of immune cells to kill Staphylococcus bacteria.
B3 increases the numbers and efficacy of neutrophils, white blood cells that can kill and eat harmful bugs.
The study, in the Journal of Clinical Investigation, could lead to a "major change in treatment", a UK expert said.
B3 was tested on Staphylococcal infections, such as the potentially fatal MRSA (Methicillin-resistant Staphylococcus aureus).
Such infections are found in hospitals and nursing homes, but are also on the rise in prisons, the military and among athletes.
The scientists used extremely high doses of B3 - far higher than that obtained from dietary sources - in their tests, carried out both on animals and on human blood.
And the researchers say there is as yet no evidence that dietary B3 or supplements could prevent or treat bacterial infections.
The researchers say B3 appears to be able to "turn on" certain antimicrobial genes, boosting the immune cells' killing power.
Prof Adrian Gombart, of Oregon State University's Linus Pauling Institute, who worked on the research, said: "This is potentially very significant, although we still need to do human studies.
"Antibiotics are wonder drugs, but they face increasing problems with resistance by various types of bacteria, especially Staphylococcus aureus.
"This could give us a new way to treat Staph infections that can be deadly, and might be used in combination with current antibiotics.
"It's a way to tap into the power of the innate immune system and stimulate it to provide a more powerful and natural immune response."
Prof Mark Enright, of the University of Bath, said: "Neutrophils  are really the front line against infections in the blood and the use of nicotinamide seems safe at this dose to use in patients as it is already licensed for use.
"This could cause a major change in treatment for infections alongside conventional antibiotics to help bolster patients immune system.
"I would like to see in patient clinical trials but cannot see why this couldn't be used straight away in infected patients."
Vitamin B3 could be the new weapon in the fight against superbugs such as MRSA, researchers have suggested.