Up to 40% of newly diagnosed cases of HIV-1 infection are late diagnoses, with a profound decrease in CD4 cell counts in many cases. One-third of these individuals do not achieve optimal CD4 cell recovery (OR) after suppressive antiretroviral treatment (ART). This retrospective/longitudinal study of poor recovery (PR) included 79 HIV-1-infected individuals with CD4 count <200 cells/mm3 (25 PR and 54 OR) before ART. After suppressive ART, 21 PR and 24 OR individuals were further analysed, including paired samples. Selected miRs and plasma inflammatory markers were determined to investigate their potential predictive/diagnostic value for poor recovery. miR-192, IL-6 and sCD14 were independently associated with CD4 recovery before ART (p = 0.031, p = 0.007, and p = 0.008, respectively). The combination of these three factors returned a good discrimination (predictive value for PR) value of 0.841 (AUC, p < 0.001). After suppressive ART, miR-144 was independently associated with CD4 recovery (p = 0.017), showing a moderate discrimination value of 0.730 (AUC, p = 0.008) for PR. Our study provides new evidence on the relationship between miRs and HIV-1 infection that could help improve the management of individuals at HIV-1 diagnosis. These miRs and cytokines signature sets provide novel tools to predict CD4 cell recovery and its progression after ART.