The initial scratch or wound caused by a bite from a carrier rodent results in mild inflammatory reactions and ulcerations. The wounds may heal initially, but reappear with the onset of symptoms. The symptoms include recurring fever, with body temperature 101–104°F (38–40°C). The fever lasts for 2–4 days, but recurs generally at 4–8 weeks. This cycle may continue for months or years. The other symptoms include regional lymphadenitis, malaise, and headache. The complications include myocarditis, endocarditis, hepatitis, splenomegaly, and meningitis.

Symptoms are different for every person depending on the type of rat-bite fever with which the person is infected. Both spirillary and streptobacillary rat-bite fever have a few individual symptoms, although most symptoms are shared. Streptobacillosis is most commonly found in the United States and spirillary rat-bite fever is generally diagnosed in patients in Africa. Rat-bite symptoms are visually seen in most cases and include inflammation around the open sore. A rash can also spread around the area and appear red or purple. Other symptoms associated with streptobacillary rat-bite fever include chills, fever, vomiting, headaches, and muscle aches. Joints can also become painfully swollen and pain can be experienced in the back. Skin irritations such as ulcers or inflammation can develop on the hands and feet. Wounds heal slowly, so symptoms possibly come and go over the course of a few months.

Symptoms associated with spirillary rat-bite fever include issues with the lymph nodes, which often swell or become inflamed as a reaction to the infection. The most common locations of lymph node swelling are in the neck, groin, and underarm. Symptoms generally appear within 2 to 10 days of exposure to the infected animal. It begins with the fever and progresses to the rash on the hands and feet within 2 to 4 days. Rash appears all over the body with this form, but rarely causes joint pain.

The streptobacillosis form of rat-bite fever is known by the alternative names Haverhill fever and epidemic arthritic erythema. It is a severe disease caused by "Streptobacillus moniliformis", transmitted either by rat bite or ingestion of contaminated products (Haverhill fever). After an incubation period of 2–10 days, Haverhill fever begins with high prostrating fevers, rigors (shivering), headache, and polyarthralgia (joint pain). Soon, an exanthem (widespread rash) appears, either maculopapular (flat red with bumps) or petechial (red or purple spots) and arthritis of large joints can be seen. The organism can be cultivated in blood or articular fluid. The disease can be fatal if untreated in 20% of cases due to malignant endocarditis, meningoencephalitis, or septic shock. Treatment is with penicillin, tetracycline, or doxycycline.

Sodoku (鼠毒) is a bacterial zoonotic disease. It is caused by the Gram-negative rod "Spirillum minus" (also known as "Spirillium minor"). It is a form of rat-bite fever (RBF).