People around the world spend hours of their daily lives using smartphones; therefore, it is important to conduct cross-cultural research on the effects of smartphone use on health and well-being as culture influences values, motivations and communication patterns. The purpose of this study was to explore 5 popular uses of the smartphone ? messaging, browsing the Internet, posting social content, reading social content, and playing games ? how they relate to anxiety and depression scores, and how they vary depending on the country of the participants: Spain, the United States, and Colombia. In all three countries the ranking of most popular uses was the same: (1) Messaging, (2) Reading social content, and (3) Browsing the Internet. In the USA, game playing contributed to anxiety scores whereas reading social content was a protective factor; regarding depression scores, text messaging was a contributing factor. In Spain, browsing the Internet contributed to anxiety scores; regarding depression scores, messaging was a contributing factor and posting social content was a protective factor. In Colombia, no specific use influenced anxiety scores; regarding depression scores, only game playing was a protective factor. Our results showed that in all the countries, problematic smartphone use contributed to anxiety scores.