This paper compares the difference between boy and girl high school students of 1st grade to 3rd grade in academic stress and depression. Using a random stratified sampling 120 girl and boy students (60 girls and 60 boys) were selected from 1st grade (n = 40), 2nd grade (n = 40) and 3rd grade (n = 40) high school students. In this study gender and grades have considered as independent variables and academic stress and depression were dependent variables. A scale for assessing academic stress (SAAS, Sinha, Sharma and Mahindra, 2001) and children depression inventory (CDI, Kovacs, 1992) were used for collecting data. To analyze of data statistics such as mean, SD, Pearson's coefficient of correlation and regression homogeneity to test of variance's homogeneity, and multivariate analyze of variance (MANOVA were used). Results showed that the effect of gender on combined dependent variables (academic stress and depression) was statistically significant (Wilk's Lambda = 0.367; F (12, 103) = 14.81, p = 0.000; Eta = 0.63); the effect of grade on combined dependent variables was statistically significant (Wilk's Lambda = 0.708; F (24, 206) = 1.98, p = 0.05; Eta = 0.16); The mutual interaction of gender and grades on combined dependent variables was not significant (Wilk's Lambda = 0.774; F 24, 206 = 1.71; p = 0.272; Eta = 0.12). The effect of gender on academic stress and its subscales (Wilk's Lambda = 0.648; F 6, 113 = 10.23; p<0.05; Eta = 0.35); and depression and its subscales (Wilk's Lambda = 0.495; F6, 113 = 19.22; p<0.05; Eta = 0.51) was statistically significant. Further the effect of grades on academic stress was significant but the effect of grade on depression was not significant. Finally the study concluded that there was a significant difference between boy and girl students in academic stress and depression.