Objective To compare the differences of clinical features between severe Mycoplasma pneumoniae pneumonia (MPP) and severe Streptococcus pneumoniae pneumonia (SPP). Methods Seventy-seven patients with severe MPP and 40 patients with severe SPP admitted to the respiratory ward of Children's Hospital Affiliated to Chongqing Medical University from January 2015 to January 2020 were retrospectively analyzed, and the general conditions, clinical manifestations, auxiliary examinations and other data of the two groups were compared. Results There were 48 boys (62.3%) in the severe MPP group with a median age of 44(24-78) months. In the severe SPP group, there were 22 boys (55.0%) with a median age of 14(9-25) months. 96.1% (74/77) of children with severe MPP and 80.0% (32/40) of children with severe SPP received antibiotics before admission (P=0.007). Compared with children with severe SPP, the proportion of fever and hyperpyrexia was higher, and the proportion of wheezing and nervous system symptoms was lower in children with severe MPP (P<0.05). The children with severe SPP were more likely to have crackles and rhonchi in the lungs, and the proportion of children with signs on both sides was higher (P<0.05). Compared with children with severe SPP, children with severe MPP had lower WBC and higher LDH levels, and were more likely to have aerated bronchus signs on chest CT (all P<0.05). There was no significant difference in bronchoscopy and routine examination results of bronchoalveolar lavage fluid between the two groups (all P>0.05). Conclusions The clinical characteristics of children with severe MPP and severe SPP are often atypical. Age, fever, hyperpyrexia, wheezing, pulmonary signs, nervous system manifestations, peripheral WBC, and peripheral blood LDH levels are helpful for clinical differentiation.