For many centuries, infectious diseases have remained an important medical and social problem of humanity. To date high rates of morbidity remain among both the adult and child population. The similarity of clinical symptoms in the onset of some infections with diseases of different nature, including connective tissue diseases, often presents difficulties for verifying the diagnosis. Different clinical manifestations of connective tissue diseases dictate the need for an extended examination of patients to clarify the nature of the disease, to determine the role of the infectious agent, if it is detected: whether it is the cause of the existing symptoms or a trigger in the development of an autoimmune disease. The article presents 2 clinical observations of the infectious debut of connective tissue diseases. Two girls, 13 years old and 5 years old, were hospitalized at the Pediatric Research and Clinical Center for Infectious Diseases with suspected acute infectious pathology. The dominant complaint was fever. In the first case cough and pain syndrome of various localization were also noted and in the second case exanthema was observed. After examination it was impossible to verify the etiological pathogen. Сonnective tissue diseases were suspected, namely, in the first clinical case systemic lupus erythematosus was suspected, in the second juvenile dermatomyositis, which were confirmed by the detection of specific autoantibodies. Clinical cases demonstrate the difficulty of establishing connective tissue diseases diagnosis due to similarity these diseases clinical picture with the onset of infectious pathology. Taking into account the dependence of the course and outcomes of connective tissue diseases on the start of specific therapy, it is necessary to increase the alertness of infectious disease doctors and pediatricians for the timely detection of this cohort of patients.