This study aimed to analyse the influence of the economic crisis on the prevalence of sexually transmitted infections (STIs) in the immigrant population compared to the native population. A cross-sectional study was conducted by reviewing 441 clinical records (329 Spanish nationals and 112 non-Spanish nationals) of individuals who, between 2000 and 2014, visited an STI clinic in Granada and tested positive for an infection. Descriptive statistical analyses were performed, and infection rates, odds ratios, and 95% confidence intervals (CIs) were calculated. The mean age was 28.06 years (SD = 8.30; range = 16–70). During the period 2000–2014, the risk of being diagnosed with an STI was higher among non-Spanish nationals than among Spanish nationals (odds ratio (OR) = 5.33; 95% CI = 4.78–6.60). Differences between both populations were less marked during the crisis period (2008–2014: OR = 2.73; 95% CI = 2.32–3.73) than during the non-crisis period (2000–2007: OR = 12.02; 95% CI = 10.33–16.17). This may be due to underreporting of diagnoses in the immigrant population. Immigrants visiting the STI clinic in Granada are especially vulnerable to positive STI diagnoses compared to the native population.