The most frequent cause of water blisters is repeated friction. Water blisters most commonly occur on the heel or the foot when someone is breaking in new shoes. When the water blisters burst, they can be painful, and those with diabetes need to be particularly careful to bandage blisters to prevent infections. Friction is, however, not the only cause of water blisters. Several other conditions can cause water blisters.

Burns are probably the second most frequent cause of water blisters. Second and third degree burns may quickly blister. Since burns of this type can cause damage to the skin, they usually require treatment with topical antibiotics to prevent infection. Large burns necessitate a trip to the doctor to help eliminate pain and to reduce risk of infection.

Some viruses can cause water blisters. Chicken pox and shingles, for example, begin with the formation of small blisters that burst after a day or so, and then begin to crust over and scab. Scabs should be watched for any signs of pus as these may indicate infection.

Allergies to substances resulting in contact dermatitis may also cause water blisters. Some people have significant allergies to detergents or cleaning chemicals that can at first show up as blisters. Blisters and/or rash may be present and should be evaluated by a doctor to rule out a viral cause. Poison oak and ivy can also cause water blisters before a rash develops.

Prickly heat, resulting from exposure to high heat in humid areas may also create water blisters. Blisters usually tend to resolve overnight, leaving behind a raised and irritated rash. As well, direct exposure to the sun, and extremely bad sunburns may blister the skin like contact burns. If the skin forms waters blisters with minimal sun exposure, this may indicate heightened skin sensitivity to the sun.

Some sexually transmitted diseases like genital warts and herpes may also form blisters prior to forming itching rashes. Blisters on the genitals should always be evaluated, since the most likely cause is herpes, which can be quite contagious. Those with herpes need to discuss reduction of risk with any potential sexual partners.