Skin reactions are commonly associated with bed bugs, which result from the saliva injected during feeding. Some individuals however, do not react to their bite, whereas others note a great deal of discomfort often with loss of sleep from the persistent biting. The most commonly affected areas of the body are the arms and shoulders. Reactions to the bites may be delayed; up to 9 days before lesions appear. Common allergic reactions include the development of large wheals, often >1cm, which are accompanied by itching and inflammation. The wheals usually subside to red spots but can last for several days. Bullous eruptions have been reported in association with multiple bed bug bites and anaphylaxis may occur in patients with severe allergies. In India, iron deficiency in infants has been associated with severe infestations. It has been suggested that allergens from bed bugs may be associated with asthmatic reactions.

Bed bugs have been implicated in the transmission of a wide variety of infectious agents, although their status as vectors is uncertain. It has been suggested that they might play a role in the spread of hepatitis B, however, experimental evidence does not support this.

Note that an irritation or bite experienced in bed may not necessarily be due to a bed bug infestation.