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Abstract Explaining the maintenance of genetic variation in fitness‐related traits within populations is a fundamental challenge in ecology and evolutionary biology. Frequency‐dependent selection (FDS) is one mechanism that can maintain such variation, especially when selection favours rare variants (negative FDS). However, our general knowledge about the occurrence of FDS, its strength and direction remain fragmented, limiting general inferences about this important evolutionary process. We systematically reviewed the published literature on FDS and assembled a database of 747 effect sizes from 101 studies to analyse the occurrence, strength, and direction of FDS, and the factors that could explain heterogeneity in FDS. Using a meta‐analysis, we found that overall, FDS is more commonly negative, although not significantly when accounting for phylogeny. An analysis of absolute values of effect sizes, however, revealed the widespread occurrence of modest FDS. However, negative FDS was only significant in laboratory experiments and non‐significant in mesocosms and field‐based studies. Moreover, negative FDS was stronger in studies measuring fecundity and involving resource competition over studies using other fitness components or focused on other ecological interactions. Our study unveils key general patterns of FDS and points in future promising research directions that can help us understand a long‐standing fundamental problem in evolutionary biology and its consequences for demography and ecological dynamics. 

1. Trade‐offs are often predicted to occur between energetically costly activities, such as somatic growth and eliciting immune responses to parasites. Although parasitism frequently reduces growth via lowered consumption, it remains unclear if the energetic demands of generating immune responses also affect the digestive physiological processes necessary for growth. Moreover, as local environmental conditions affect energetic investment towards growth and immune responses, the extent of any digestive–immune response trade‐offs may vary among populations and not be fixed at the species‐level. 2. To test these ideas, melanisation – a general innate immune response – was first induced in damselfly larvae (Enallagma vesperum) from two populations. The study then quantified growth and consumption rates, assimilation and production efficiencies, and daily metabolic rates to determine if digestive–immune response trade‐offs were present and, if so, whether they differed between populations. 3. There was no evidence of any trade‐offs between immune responses and digestive physiology components in either population. However, the results did show that populations differentially allocated energy towards different digestive physiology components after an immune response was elicited: one population increased their relative consumption and daily metabolic rates, while the other population had lower assimilation efficiencies and consumption rates. 4. Although researchers lack a mechanistic understanding of the observed population‐level differences, these results suggest that accounting for population‐level variation in digestive physiology and immune responses is critical to inferences about how immunological defences to parasitism may affect the ability for organisms to both acquire and utilise resources.