Some people infected with LCMV do not become ill. For infected persons who do become ill, onset of symptoms usually occurs 8-13 days after being exposed to the virus. A characteristic biphasic febrile illness then follows. The initial phase, which may last as long as a week, typically begins with any or all of the following symptoms: fever, malaise, lack of appetite, muscle aches, headache, nausea, and vomiting. Other symptoms that appear less frequently include sore throat, cough, joint pain, chest pain, testicular pain, and parotid (salivary gland) pain. Following a few days of recovery, the second phase of the disease occurs, consisting of symptoms of meningitis (for example, fever, headache, and a stiff neck) or characteristics of encephalitis (for example, drowsiness, confusion, sensory disturbances, and/or motor abnormalities, such as paralysis). LCMV has also been known to cause acute hydrocephalus (increased fluid on the brain), which often requires surgical shunting to relieve increased intracranial pressure. In rare instances, infection results in myelitis (inflammation of the spinal cord) and presents with symptoms such as muscle weakness, paralysis, or changes in body sensation. An association between LCMV infection and myocarditis (inflammation of the heart muscles) has been suggested.

During the first phase of the disease, the most common laboratory abnormalities are a low white blood cell count (leukopenia) and a low platelet count (thrombocytopenia). Liver enzymes in the serum may also be mildly elevated. After the onset of neurological disease during the second phase, an increase in protein levels, an increase in the number of white blood cells or a decrease in the glucose levels in the cerebrospinal fluid (CSF) is usually found.

Previous observations have shown that most patients who develop aseptic meningitis or encephalitis due to LCMV recover completely. No chronic infection has been described in humans, and after the acute phase of illness, the virus is cleared. However, as in all infections of the central nervous system, particularly encephalitis, temporary or permanent neurological damage is possible. Nerve deafness and arthritis have been reported. Infection of the human fetus during the early states of pregnancy may lead to developmental deficits that are permanent.

LCM is usually not fatal. In general, mortality is less than 1%.