We assessed the secular trends in the serum lipid levels in Shanghai residents from 1973 to 1999. Data from four independent, cross-sectional, population-based surveys were used to analyze the trends in serum lipid levels from 1973 to 1999. A standard protocol was applied across each survey in at least three independent surveys which were separated a 10-year study period. A total of 10733 (1385, 3302, 2399, and 3647 subjects who had complete data on serum lipids in 1973–1974, 1982, 1983 and 1997–1999, respectively) Shanghai residents aged from newborn to 80 years old were enlisted at random. Serum lipid levels were measured in a single laboratory throughout the entire study period. A non-significant increase was noted from 1973–1974 to 1982–1983 in the serum lipid profiles; however, a significant increase was observed from 1982–1983 to 1997–1999 in most of the age groups of both sexes. Mean serum total cholesterol (TC) levels increased significantly ( < 0.05) over the entire study period (overall period covered: 1973–1999) in most age groups of both sexes. In males, the changes were from 7.3% to 23.2% and in females, from 9.0% to 21.6%, except in umbilical blood samples and in females over 60 years where insignificant results were observed. Similar trends were observed in the mean serum triglyceride (TG) and the mean serum low-density lipoprotein cholesterol (LDL-c) levels, both in females and males. The majority show an upward trend. As for TGs, the changes were from 27.5% to 82.7% in males and from 13.2% to 54.6% in females. As for LDL-c the changes were from 34.9% to 71.0% in males and from 31.9% to 63.6% in females. Mean serum high-density lipoprotein cholesterol (HDL-c) levels were decreased significantly from 1982–1983 to 1997–1999, with the changes from -13.2% to -38.6% in males and from -9.8% to -21.7% in females. The ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-c) increased dramatically during this period because of a concurrent decline in the levels of HDL-c and the increase in the levels of TC. The prevalence of hypercholesterolemia (To achieve the normal range of serum TC and TG in healthy people of Shanghai, we determined the cut-off point in the cumulative frequency curve as the 95% percentile of the data collected by the survey in 1973–1974. The results show that the 95% cut-off point for TC was 220 mg/dL, while for TG, it was 160 mg/dL.) increased significantly ( < 0.05). In males aged 20 to 40 years old, the prevalence of hypercholesterolemia was from 1.6% to 7.79%, and in ages> 40 it was from 5.5% to 11.57%. In females, it was 0 to 4.68% and 6.5% to 16.2%, respectively. In general, the trends in the levels of TC, TG and LDL-c were increasing and trends in the levels of HDL-c were decreasing in most age groups, especially, in the younger age group of Shanghai residents from 1980s to 1990s. These worrying findings are significant for its public health implications. Health education and health promotion are necessary to prevent the disease prevalence from rising in the Chinese population.