Objective: To understand the current status and associated factors of comorbidity of common illnesses among primary and middle school students in Shanghai, so as to provide a reference for improving the pathogenic environment and preventing the occurrence of comorbidity of common illnesses. Methods: From September to November 2021, a stratified cluster sampling method was used to select 30 331 middle school students from 112 schools in 16 districts of Shanghai, each with 2 primary schools, 2 junior high schools, 2 high schools and 1 vocational high school. Elementary school students, their health status and influencing factor questionnaires were analyzed. Results: The detection rate of two or more common diseases such as myopia, overweight and obesity, high blood pressure, and abnormal spinal curvature among primary and secondary school students in Shanghai was 38.91%, of which 29.64% of primary and secondary school students had two diseases at the same time, and 9.19% had three diseases, 0.09% had 4 diseases. The detection rate of comorbidity was higher in boys (44.12%) than in girls (33.40%), and higher in junior high school students (40.40%) than in high school students (38.58%) and primary school students (38.01%). The differences were statistically significant (χ2=366.44, 50.33, P<0.01). Multifactor Logistic regression analysis showed that girls sometimes supervise themselves and often remind themselves that their sitting and standing postures were negatively correlated with the common comorbidities of primary and secondary school students (OR=0.64, 0.93, 0.90); junior middle school students and watching TV/d ≥1 h, using computers for ≥1 h/d, and using mobile electronic devices for >1 h/d were positively correlated with the comorbidity of common diseases among primary and secondary school students (OR=1.07, 1.10, 1.06, 1.10) (P<0.05). Conclusions The prevalence of comorbidity of common illnesses among primary and middle school students in Shanghai is not optimistic, which might be associated with combined effects of various external environmental factors. Targeted intervention should be implemented to effectively prevent the occurrence of comorbidities among students.