Background Public health awareness can help prevent illness and result in earlier intervention when it does occur. For this reason, health promotion and disease awareness campaigns have great potential to alleviate the global burden of disease. Global Public Health Days (GPHD) are frequently implemented with this intent, but research evaluating their effectiveness, especially in the developing world setting, is scant. Objectives We aimed to evaluate the impact of four GPHDs (World Cancer Day, World Diabetes Day, World Mental Health Day, World AIDS Day) on online health information seeking behaviour (OHISB) in five Central and South American (CSA) countries which differ in their stage of economic development and epidemiological transition (Uruguay, Chile, Brazil, Colombia, Nicaragua). Methods Google Trends data was used as a 'surrogate' of OHISB. This was measured on the 28 days leading up to the GPHD, on the date of the GPHD, and on the seven days following it. The Joinpoint regression programme was used to perform a time trend analysis on the Google Trends data. This allowed us to identify statistically significant time points of a change in trend, which reflect significant 'changes' to OHISB. Results GPHDs were inconsistently effective at influencing internet search query activity in the studied countries. In situations where an effect was significant, this impact was consistently short-term, with Relative Search Volume level returning to precampaign levels within 7 days of the GPHD. Conclusions Our findings imply the need to revise GPHDs or create alternative health awareness campaigns, perhaps with a more long-term approach and tailored to the specific health needs of the CSA population. Developing effective preventive strategies is vital in helping combat the rising threat of NCDs in this region.